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； ObjectiveTo explore the effect of direct-acting antiviral treatment on renal function in patients with chronic hepatitis C. MethodsA total of 123 HCV-infected patients receiving DAAs treatment at the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2021 were included in this study. To explore the renal function in patients with chronic hepatitis C treated with direct-acting antivirals， serum creatinine values were collected before， during and after the treatment， which were used to estimate the eGFR by the MDRD equation to assess the changes in renal function. ResultsOf the 123 patients enrolled， 67.5%（n=83）were male， and the mean age of participants was （50±11） years old. The mean follow-up period was 24 weeks . Comorbidities included cirrhosis in 26.8%， and diabetes in 10.6%. Meanwhile， 11.4% of the cohort had eGFR < 60 mL/（min ·1.73 m2）， 33.3% of the cohort had eGFR 60 to 90 mL/（min ·1.73 m2）， and 55.3% had eGFR≥90 mL/（min ·1.73 m2）. No decrease in renal function was seen among all the HCV-infected patients at the end of treatment or the follow-up period after treatment. However， compared with the eGFR at the baseline， eGFR in CKD2 patients in the follow-up period was improved 【（88.65±15.52） mL/（min ·1.73 m2）vs （78.12 ±7.60） mL/（min ·1.73 m2）， P< 0.001】. And 14.6% （n=18） of patients experienced progressive deterioration of renal function. Logistic regression analysis showed that diabetes could predict the deterioration of renal function （OR=4.663， P=0.016）. ConclusionsOur study shows renal function is not impair among HCV-infected patients following DAAs treatment， and renal function in CKD2 patients have improvements. However， HCV-infected patients with diabetes mellitus are at a high risk of renal impairment and closely monitoring of renal function is still needed.
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Objective@#To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients.@*Methods@#A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data.@*Results@#80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment.@*Conclusion@#In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.
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Objective@#To investigate the effects of direct-acting antiviral agents (DAA) therapy on the frequency of myeloid-derived suppressor cells (MDSC) and their subset of monocytic myeloid-derived suppressor cells (M-MDSC) in chronic hepatitis C (CHC) patients.@*Methods@#A total of 32 treatment-naive CHC patients and 16 healthy controls were recruited at Third Affiliated Hospital of Sun Yat-Sen University from June 2016 to June 2017. The peripheral blood mononuclear cells (PBMC) were separated from the peripheral blood of patients with CHC before DAA therapy, at four weeks after DAA therapy, at 12 weeks after DAA therapy and 12 weeks after the end of DAA therapy. The frequencies of MDSC and M-MDSC were detected by the flow cytometer. The t test, U test and chi-square test was employed to analyze the data.@*Results@#All the 32 treatment-naive patients achieved the rapid virological response and no virological breakthrough was observed. Before DAA therapy, the frequency of MDSC in CHC patients was 2.18%, which was higher than healthy individuals (0.60%; Z=-4.593, P<0.01), and positively correlated with the plasma levels of hepatitis C virus (HCV) RNA (r=0.688, P<0.01) and aspartate aminotransferase (r=0.735, P<0.01). After four weeks of DAA therapy, the frequency of MDSC decreased significantly to 1.07%, with no statistical significance compared to the controls (Z=-1.221, P>0.05). However, at 12 weeks after DAA therapy, the MDSC frequency increased, with statically significance compared to the controls (1.64% vs 0.60%, Z=-3.117, P=0.002). At 12 weeks after the end of DAA therapy, the MDSC frequency had decreased to 1.29% again, with no statistical significance compared to the controls (Z=-1.387, P=0.664). The changes of M-MDSC frequency were slightly different. Before DAA therapy, the frequency of M-MDSC in CHC patients was higher compared to healthy controls (1.66% vs 0.81%, Z=-2.745, P<0.01). The frequencies of M-MDSC were 0.91%, 1.09% and 1.10% at four, 12 weeks after DAA and 12 weeks after the end of DAA therapy, respectively. The differences were not statistically significant compared to the controls (Z=-0.589, -1.028 and -0.486, respectively, all P>0.05).@*Conclusion@#Immune status of the peripheral MDSC and M-MDSC can return to normal after DAA therapy in CHC patients.
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Objective To investigate the effects of direct-acting antiviral agents (DAA) therapy on the frequency of myeloid-derived suppressor cells (MDSC) and their subset of monocytic myeloid-derived suppressor cells (M-MDSC) in chronic hepatitis C (CHC) patients.Methods A total of 32 treatment-naive CHC patients and 16 healthy controls were recruited at Third Affiliated Hospital of Sun Yat-Sen University from June 2016 to June 2017.The peripheral blood mononuclear cells ( PBMC) were separated from the peripheral blood of patients with CHC before DAA therapy , at four weeks after DAA therapy , at 12 weeks after DAA therapy and 12 weeks after the end of DAA therapy.The frequencies of MDSC and M-MDSC were detected by the flow cytometer.The t test, U test and chi-square test was employed to analyze the data.Results All the 32 treatment-naive patients achieved the rapid virological response and no virological breakthrough was observed . Before DAA therapy, the frequency of MDSC in CHC patients was 2.18%, which was higher than healthy individuals (0.60%; Z＝-4.593, P＜0.01), and positively correlated with the plasma levels of hepatitis C virus (HCV) RNA (r＝0.688, P＜0.01) and aspartate aminotransferase (r＝0.735, P＜0.01).After four weeks of DAA therapy, the frequency of MDSC decreased significantly to 1.07%, with no statistical significance compared to the controls ( Z＝-1.221, P＞0.05).However, at 12 weeks after DAA therapy , the MDSC frequency increased , with statically significance compared to the controls (1.64%vs 0.60%, Z＝-3.117, P＝0.002).At 12 weeks after the end of DAA therapy , the MDSC frequency had decreased to 1.29%again, with no statistical significance compared to the controls ( Z ＝-1.387, P ＝0.664).The changes of M-MDSC frequency were slightly different.Before DAA therapy, the frequency of M-MDSC in CHC patients was higher compared to healthy controls (1.66%vs 0.81%, Z＝-2.745, P＜0.01).The frequencies of M-MDSC were 0.91%, 1.09% and 1.10% at four, 12 weeks after DAA and 12 weeks after the end of DAA therapy , respectively.The differences were not statistically significant compared to the controls (Z＝-0.589,-1.028 and -0.486, respectively, all P＞0.05).Conclusion Immune status of the peripheral MDSC and M-MDSC can return to normal after DAA therapy in CHC patients.
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Objective@#To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients.@*Methods@#An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups.@*Results@#Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred.@*Conclusion@#DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.
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Objective@#To investigate the clinical effect and safety of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in the treatment of previously untreated HBeAg-positive chronic hepatitis B (CHB) patients with a high viral load.@*Methods@#A retrospective analysis was performed for the clinical data of 152 HBeAg-positive CHB patients with a high viral load (HBV DNA≥106 IU/ml) who were firstly treated with ETV (ETV group) or TDF (TDF group), with 76 patients in each group. The serum levels of alanine aminotransferase (ALT), HBV DNA, HBeAg, anti-HBe, creatinine, and creatine kinase were measured at baseline, and the patients were followed up and evaluated at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 of treatment. The Kaplan-Meier survival curves were used to analyze cumulative complete virologic response, HBeAg seroconversion, and ALT normalization rate. The Cox proportional hazards regression model was used to identify the influencing factors for virologic response. P < 0.05 was considered statistically significant.@*Results@#There were no significant differences in ALT normalization rate between the ETV group and the TDF group at weeks 4, 12, 24, 48, 72, and 96 of treatment (18.1%/55.6%/83.3%/90.3%/93.1%/97.2% vs 16.0%/53.6%/75.4%/94.2%/100%/100%, P > 0.05). There were also no significant differences in virologic response rate between the ETV group and the TDF group at weeks 48 and 96 of treatment (89.5%/97.3% vs 93.4%/98.7%, P > 0.05). The multivariate analysis showed that the baseline parameters were not predictive factors for virologic response. At week 48 of treatment, the TDF group had a significantly higher HBeAg seroconversion rate than the ETV group (14.5% vs 3.9%, P = 0.048); at week 96 of treatment, there was no significant difference in HBeAg seroconversion rate between the two groups (15.8% vs 7.9%, P = 0.132). The Kaplan-Meier survival analysis showed that there were no significant differences between the two groups in cumulative ALT normalization rate, cumulative HBV DNA undetectable rate, and cumulative seroconversion rate. Only one patient in the ETV group experienced virologic breakthrough from weeks 60 to 72 of treatment, and there were no serious adverse reactions.@*Conclusion@#TDF and ETV had similar clinical effects, HBeAg seroconversion rate, and safety in previously untreated HBeAg-positive CHB patients with a high viral load.
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Objective To investigate the correlation between the frequency of myeloid-derived suppressor cells (MDSC) and the frequency of regulatory T cells (Treg) in the peripheral blood in patients with chronic hepatitis B (CHB) and its clinical significance.Methods A total of 45 CHB patients including 23 mild-to-moderate CHB patients,22 severe CHB patients,and 15 healthy controls were enrolled.The frequencies of MDSC and Treg in the peripheral blood were studied using flow cytometry and its correlation with clinical data was analyzed by Sepearman correlation analysis.Results The median frequency of MDSC in CHB patients was 0.414％,which was significantly higher than that in healthy controls 0.226％ (Z=-2.356,P=0.018 9).The frequency of MDSC in CHB patients was negatively correlated with the level of alanine transaminase (ALT) and aspartate transaminase (AST) (r=-0.480,-0.478; both P＜0.01),but had no relations with hepatitis B virus (HBV) viral load (r=-0.049,P=0.75).An increase frequency of MDSC was observed in CHB patients with an ALT of 5 × upper limits of normal (ULN) or less or AST of 3 × ULN or less.The frequency of MDSC in CHB patients was positively correlated with that of Treg (r =0.345,P =0.02).Conclusions The activation and proliferation of MDSC may facilitate and maintain HBV persistent infection.The change of the frequency of MDSC is in line with that of Treg,indicating that immunosuppressive functions of MDSC may be related with the development of Treg in CHB.
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Objective To investigate the efficacy of pegylated interferon (PEG-IFN)+ ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC),and to evaluate the predictors of treatment response.Methods One hundred and thirty CHC patients treated with PEG-IFN a-2a 180 μg weekly or PegIFNα-2b 80 μg weekly plus RBV 900-1200 mg/d for 48 weeks in Guangdong Province were enrolled.The clinical data including age,gender,body mass index (BMI),spleen index (SPI),the diameter of portal vein (PV),hepatitis C virus (HCV) genotype,HCV RNA level were collected at baseline,week 4,12,24,48 of treatment and week 24 of follow-up.Patients obtained sustained virological response (SVR) were compared to those with non-sustained virological response (NSVR).The related factors of SVR were analyzed.The data were compared by t test,chi square test or Logistic regression.Results The total SVR rate was 84％ (109/130),among which rapid virological response ( RVR ),early virological response ( EVR ),and end-of-treatment virological response (ETVR) were 21％ (27/130),72％ (94/130) and 93％ (121/130),respectively.HCV genotype was determined in 70 patients and the SVR rate was 82 ％ (45/55) in the genotype 1 patients and 87％ (13/15) in the genotype non-1 patients.Age,baseline HCV RNA,BMI and SPI were all negatively associated with SVR rate (regression coefficient＜0,all OR＜1,all P＜0.05),while EVR and total cumulative treatment dose of RBV were positively associated with SVR rate (regression coefficient＞0,both OR＞ 1,both P＜0.05).However,RVR,PV and total cumulative treatment doses of PEG-IFN were not associated with SVR rate (P＞0.05).Conclusions The SVR rate of PEG-IFN plus RBV combined treatment is high in CHC patients and more than 80％ of patients can be cured.However,the SVR rates are lower in patients elder than 35 years,with previous treatment failure history,baseline HCV RNA＞6 × 105 IU/mL,BMI＞26 kg/m2,SPI＞40 cm2,or the total cumulative treatment doses of RBV less than 80 ％ of standard dose.
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Objective To investigate the effect of Peg-Interferon α-2a therapy on the quality of life (QOL) of patients with chronic hepatitis C,and to evaluate the effect of healthcare insurance policy in Guangzhou city on these patients.Methods Totally 102 patients with chronic hepatitis C were enrolled.Forty-two patients (group A) were treated with Peg-Interferon α-2a plus ribavirin whose medical expenses were covered by medical insurance; 30 patients (group B ) received the same therapy but at their own expenses ; and the other 30 patients ( group C) were not treated with Peg-Interferon α-2a.QOL of patients in three groups were investigated using the general quality of life inventory questionnaire (GQOLI-74) before and after Peg-Interferon α-2a treatment.Wilcoxon test was used to compare on all scales and total scores before and after treatment in each group,and Kruskal-Wallis test was performed to compare on all scales and total scores among three groups.Results Before treatment,the physical function,psychological function,social function,material life and total score of group A were 55.3,58.8,61.9,60.6 and 58.5 ; those of group B were 57.5,60.4,61.1,55.2 and 58.3; those of group C were 58.6,60.3,57.5,54.8 and 56.4.There was no statistic difference on all scales and total scores among three groups (Z =- 1.177,- 0.846,- 1.062,-0.377 and - 1.085,P ＞ 0.05).After treatment,group A had higher QOL on all scales (67.1,76.4,68.1,70.1) and total score (72.6) than group C (54.6,54.0,53.3,57.5 and 54.6,P ＜0.01) ; group B had higher QOL (P ＜0.05) on three scales (65.1,65.0 and 69.6) and total score ( 64.3 ) except material life ( 56.3 ) than group C ; group A had higher QOL on psychological function,material life and total score than group B ( P ＜ 0.05 ).Conclusions QOLs of chronic hepatitis C patients treated with Peg-Interferon α-2a are higher than those without Peg-Interferon α-2a treatment.Patients whose medical expenses are covered by medical insurance may have higher QOLs than those at their own expenses.
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Objective To study the expression of signaling lymphocytic activation molecule (SLAM)CD150 in peripheral blood mononuclear cells(PBMCs)isolated from adult non-responders to recombined yeast gene hepatitis B vaccine.Methods A total of 202 cases were recruited.All these subjects had been immunized with recombined yeast gene hepatitis B vaccine for more than one standard scheme in two years(from Sep 2007 to Dec 2009)and remained negative for hepatitis B markers(HBsAg,anti-HBs,HBeAg,anti-HBe and anti-HBc).After recruitment,all 202 subjects received another standard scheme(0,1 and 6 month)revaccination.The blood samples were collected 7 months later after the first injection of revaccination to detect anti-HBs titer.The PBMCs were isolated from 18 adult non-responders(anti-HBs titer0.05).After phytohaemagglutinin (PHA)stimulation,the percentage of CD150-positive PBMCs was also significantly higher in non-responders (39.21%±7.37%)than responders(23.18%±12.68%)(t=2.2835,P<0.05).CD150 expressions in both PBMCs and CD3+CD4+T cells were negatively correlated with anti-HBs titer after rHBsAg stimulation (r=-0.726,P<0.05).Conclusion Activation of CD150 may contribute to the non-response to hepatitis B vaccine.
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Objective To investigate the revaccination efficacy of different dosages of hepatitis B vaccine among adult non-and hyporesponders so as to improve the protection rate of hepatitis B vaccination.Methods The healthy adults who were immunized with hepatitis B vaccine at least one standard scheme in two years and negative for hepatitis B markers were enrolled in this randomized and open-label study.The hepatitis B vaccine was injected intramuscularly in the deltoid muscle on an upper arm according to routine schedule (month 0,1,6).The adults were randomly given four different dosages:73 in group A were given hepatitis B vaccine 10 μg (made in China) each time;69 in group B were given hepatitis B vaccine (made in China) 20 μg each time;70 in group C were given gene recombinant yeast hepatitis B vaccine (Engerix) 20 μg each time and 48 in group D were given gene recombinant yeast hepatitis B vaccine 40 μg each time.The serum anti-HBs was tested before and 1,2,8,12 months after the first injection.The comparison of means was done by one-factor analysis of variance and the comparison of rates was done by chi square test.Results The anti-HBs positive rates were the highest at months 8 of re-immunization in group B,C and D,which were 68.1%,70.0% and 77.1%,respectively,and were all higher than that in group A (53.4%)(χ2=21.465,P＜0.01).The anti-HBs positive rate increased in group B,C and D with increasing immunized times and over time,but there was no significant difference;it went down at 12 months after re-immunization.The anti-HBs positive rates at 1,2,8 and 12 months after re-immunization in group A were 8.2%,19.2%,53.4% and 43.8%,respectively and differences were significant (χ2=53.07,P＜0.01).The anti-HBs levels in group B,C and D were all higher than that of group A(F=7.551,P＜0.05) at month 12 of re-immunization.There were no significant differences of anti-HBs levels at different re-immunization time points in group B,C and D.Conclusion Revaecination of hepatitis B vaccine can induce immune responses and increasing dosages can improve the immune efficacy in non- and hyporesponders.
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0.05).The death rate of cases with pneumonia combined with ascites was higher than that of cases with ascites only(?2=4.894,P=0.027) and cases without ascites and infections(?2=9.260,P=0.002).Unfavorable prognosis was found in cases with Enterococcus faecium isolated before OLT.CONCLUSIONS Severe lung infection before OLT is one of the main reasons of death.It is important to grasp characteristics of infection,evaluate risk fully,control infections and screen cases strictly before OLT to improve survival rate.
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Objective To study the relationship of hepatitis and pregnan cy .Methods 49 cases with viral hepatitis of pregnancy were analyze d and compared with viral hepatitis of non-pregnant cases.Results Most of the hepatitis following pregnancy were HBV,with the increment of preg nant weeks,the incidence and mortality rates of hepatitis were increased.PT was remarkably prolonged and ALB lowered in 49 cases.Complications of hepatic enceph alopathy and hepto-renal syndrome were more,the incidence and fatality rates of severe hepatitis were higher than that in healthy group (P