； 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.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Objective:To explore the effects of direct antiviral agent (DAAs) on the frequency of peripheral blood mononuclear cells and their activating factors sCD14s and CD163 in patients with chronic hepatitis C.Methods:Data of 15 treatment-naive chronic hepatitis C patients and 10 healthy controls were collected. Patients with chronic hepatitis C were treated with DAAs for 12 weeks. Blood samples were collected at 0, 4 and 12 weeks respectively, and blood samples of healthy controls were used as controls. Flow cytometry was used to detect the frequency of classical CD14 ++CD16 - mononuclear cells and pro-inflammatory CD14 +CD16 + mononuclear cells in peripheral blood. Serum sCD14s and sCD163 were detected by enzyme-linked immunosorbent assay. The comparison between the two groups was performed by t-test. The comparison between multiple groups was performed by analysis of variance, and further pairwise comparison was performed by LSD-t test. Results:Prior DAAs treatment, peripheral blood CD14 +CD16 + mononuclear cell frequency (18.49% ± 1.54% vs. 10.65% ± 0.83%), serum sCD14s [(64 407.38 ± 5778.49) pg/ml vs. (28 370.76 ± 2 357.68 ) pg/ml] and sCD163 [(22 853.80 ± 4 137.61) pg/ml vs. (2 934.41 ± 223.31) pg/ml] were all higher than healthy controls ( P < 0.05), while the frequency of CD14 ++CD16 - mononuclear cells in peripheral blood was lower than healthy controls (59.14%±0.54% vs. 72.75%±1.31%, P < 0.01). During DAAs treatment, CD14 +CD16 + mononuclear cells frequency, serum sCD14 and sCD163 were all decreased significantly. After 12 weeks of treatment, CD14 +CD16 + mononuclear cells had decreased to nearly normal level (12.42% ± 1.60% vs. 10.65% ± 0.83%, P > 0.05), and serum sCD14 and scd163 were still higher than those of healthy controls [sCD14: (44 390.06 ± 3 330.17) pg / ml vs. (28 370.76 ± 2 357.68) pg/ml, Scd163: (11 494.79 ± 1 836.97) pg / ml vs. (2 934.41 ± 223.31) pg / ml, P < 0.01], while the frequency of CD14 ++CD16 -mononuclear cells had gradually increased during the course of treatment and neared healthy control level after 12 weeks of treatment. There was no statistically significant difference between the two groups (71.54) % ± 2.99% vs. 72.75% ± 1.31%, P > 0.05). Conclusion:DAAs therapy can reduce the activation of peripheral blood mononuclear cells in patients with chronic hepatitis C.

Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(1TT)and modified 1TT(mITT)populations were used in the analysis. Results:One hundred forty patients were included,among whom 90.0％(126/140)were newly diag-nosed,9.3％(13/140)had compensated cirrhosis,92.9％(130/140)received 12 weeks of treatment,and 7.1％(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4％(108/112),and at the end of treatment was 100％(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4％)patients,and none were considered to be drug-related.Sixty-six(47.1％)patients did not return to receive the HCV RNA test at 12 weeks post-treatment. Conclusions:The rate of SVR12 was consistent with Phase Ⅲ clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.

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.

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.

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.

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.

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.