To investigate the correlation between neutropenia (ANC) incidence and infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C.A retrospective cohort study of 399 patients treated with peginterferon and ribavirin derived from database of Department of Infectious Diseases, the Second Affiliated Hospital, Harbin Medical University was conducted. The incidence of infections and their relation with ANC were investigated. Potential risk factors for infection were identified by multivariate analysis.During treatment, neutropenia (ANC < 1.50 × 10(9)/L) occurred in 251 patients. Among which, mild neutropenia [ANC: (> 0.75 - < 1.50) × 10(9)/L], moderate neutropenia [ANC: (0.50 - 0.75) × 10(9)/L] and severe neutropenia (ANC < 0.50 × 10(9)/L) occurred in 132 patients, 103 patients and 16 patients, respectively. A total of 80 infections (20.1%) occurred, among which, 14 infections were defined as severe. There was no significant difference in infection rate between patients with and without neutropenia (19.9%, 50/251 vs 20.3%, 50/251; χ(2) = 0.007, P = 0.933). There was no significant difference in infection rate between patients with and without peginterferon dose reduction (21.5%, 31/144 vs 19.2%, 49/255; χ(2) = 0.307, P = 0.580). In multivariate logistic regression analysis, the independent factors associated with infection were age (P = 0.021), diabetes (P = 0.004) and cirrhosis (P = 0.012).Infections during treatment with peginterferon alfa and ribavirin for chronic hepatitis C are irrelevant to neutropenia. The independent factors associated with infection are age, diabetes and cirrhosis.
Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV) infection. Some evidence has suggested the potential role of silent information regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate the effect of HCV core protein on expression of SIRT1 of liver sinusoidal endothelial cell (LSEC) and function of LSEC. LSECs were co‐cultured with HepG2 cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were used as controls. After co‐culture, the activity and expression levels of mRNA and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit, real time‐PCR (RT‐PCR), Western blot, respectively. The levels of adiponectin receptor 2 (AdipoR2), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by Western blot. Cluster of differentiation 31 (CD31), CD14, and von Willebrand factor (vWf) of LSECs was performed by flow cytometry. The level of reactive oxygen species (ROS) was assayed. Malondialdehyde (MDA), superoxide dismutase (SOD), adiponectin, nitric oxide (NO), and endothelin‐1 (ET‐1) levels in the co‐culture supernatant were measured. The co‐culture supernatant was then used to cultivate LX‐2 cells. The levels of α‐smooth muscle actin (ASMA) and transforming growth factor‐β1 (TGF‐β1) protein in LX‐2 cells were measured by Western blot. Compared with LSEC co‐cultured with HepG2 cells group, in LSEC co‐cultured with HepG2‐core cells group, the activity and expression level of mRNA and protein of SIRT1 reduced; the level of adiponectin reduced and the expression level of AdipoR2 protein decreased; ROS levels increased; the expression level of eNOS, VEGF protein decreased; and the expression level of CD14 decreased; the expression level of vWf and CD31 increased; NO and SOD levels decreased; whereas ET‐1 and MDA levels increased; the levels of ASMA and TGF‐β1 protein in LX‐2 cells increased. SIRT1 activator improved the above‐mentioned changes. HCV core protein may down‐regulate the activity and the expression of SIRT1 of LSEC, then decreasing synthesis of adiponectin and the expression of AdipoR2, thus inducing contraction of LSEC and hepatic sinusoidal capillarization and increasing oxidative stress, ultimately cause hepatic stellate cell (HSC) activation. Treatment with SIRT1 activator restored the function of LSEC and inhibited the activation of HSC.
To investigate the impact of age and sex on virologic responses rates to peginterferon alfa-2a and ribavirin treatment in patients with chronic hepatitis C.The medical records of 449 chronic hepatitis C patients, treated with peginterferon and ribavirin in Department of Infectious Diseases, the Second Affiliated Hospital, Harbin Medical University, were retrospectively analyzed. These patients were divided into three groups according to age: patients < 40 years (n = 131), patients 40 - 50 years (n = 131) and patients > 50 years (n = 187). The virologic response rates, the incidences of side events, and the rates of patients receiving ≥ 80% of planned peginterferon alfa-2a or ribavirin dose were compared between male and female patients in the three groups. The influential factors on sustained virologic response (SVR) of patients were studied by multivariate analysis.For genotype 1, in patients < 40 years group, the SVR rate of female was significantly higher than that of male (75.0%, 30/40 vs 54.0%, 27/50; P < 0.05); in patients 40-50 years group, there was no significant difference in the SVR rate between male and female (51.0%, 25/49 vs 53.7%, 22/41; P > 0.05); in patients > 50 years group, the SVR rate of female was significantly lower than that of male (31.1%, 19/61 vs 50.7%, 34/67; P < 0.05). For genotype 2, there were no significant differences in virologic response rates between male and female in the three groups. The incidence of adverse events of patients aged < 40 years group, 40 - 50 years group, > 50 years group, were 51.1% (67/131), 51.1% (67/131), and 70.6% (132/187), respectively, and the incidence of adverse events of patients aged > 50 years was significantly higher than those of other groups (P < 0.001). For genotype 1, in patients > 50 years group, the rate of patients receiving ≥ 80% of planned ribavirin dose of female was significantly lower than that of male (42.6%, 26/61 vs 62.7%, 42/67; P < 0.05). In multivariate analysis, the independent factors associated with SVR of patients aged > 50 years were sex (P = 0.013), genotypes (P = 0.002), cirrhosis (P = 0.004), ≥ 80% of planned ribavirin dose (P = 0.008) and presence of rapid virologic response (RVR) (P = 0.001).For genotype 1 patients, in patients < 40 years group the SVR rate of female is higher than that of male; in patients 40 - 50 years group, male and female share similar SVR rates; in patients > 50 years group the SVR rate of female is lower than that of male. Age and sex has no impact on virologic responses rates for genotype 2 patients.
Abstract Objective: To study the virological features of patients coinfected with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the efficacy of combination therapy with peginterferon α‐2a and ribavirin in these patients. Methods: The epidemiological and virological data of 50 patients coinfected with HBV and HCV were analysed. The virological response rates of patients treated with peginterferon α‐2a and ribavirin between the HBV and HCV coinfection group and the HCV monoinfection group were compared. Results: HCV‐dominant virus strains accounted for 92.0% of the 50 coinfected individuals, and HCV‐ and HBV‐dominant virus strains accounted for the remaining 8.0%. The HBV DNA level of the patients coinfected with HBV and HCV was 4.6±0.9 log 10 copies/ml, which was significantly lower than that in the HBV monoinfection group (5.9±1.2 log 10 copies/ml) ( t =5.964, P <0.01). The HBeAg‐positive rate (12.0%, 6/50) of the coinfection group was significantly lower than (45.3%, 19/42) that of the HBV monoinfection group (χ 2 =12.743, P <0.01). The partial early virological response (pEVR) rate and the end‐of‐treatment virological response (ETVR) rate (50.0%, 15/30; 90.0%, 27/30) of patients with genotype 1 in the coinfection group were significantly higher than those (16.0%, 4/25; 56.0%, 14/25) in the HCV monoinfection group (χ 2 =6.971, P =0.008; χ 2 =8.307, P =0.004). The relapse rate (55.6%, 15/27) of patients with genotype 1 in the coinfection group was significantly higher than that (21.4%, 3/14) in the HCV monoinfection group (χ 2 =4.360, P =0.037). The sustained virological response (SVR) rate (40.0%, 12/30) of patients with genotype 1 in the coinfection group was compared with that of the HCV monoinfection group (44.0%, 11/25) (χ 2 =0.090, P =0.765). There was no significant difference in the on‐treatment virological response, ETVR, SVR and relapse rates between two groups for patients with genotype 2. The incidence of side effects (30%, 15/50) of patients in the coinfection group was significantly higher than that (13%, 6/46) in the HCV monoinfection group (χ 2 =4.031, P =0.045). The reactivation rate of HBV DNA (33.3%, 9/27) with HCV SVR was significantly higher than that of patients without SVR (8.7%, 2/23) (χ 2 =4.393, P =0.036). Conclusions: The replication of HBV was suppressed, and HCV was the dominant virus strain. Compared with HCV‐monoinfected patients, pEVR, ETVR and relapse rates of patients with genotype 1 in the coinfection group were high, while they shared similar SVR rates. HBV and HCV coinfection had no impact on the rate of virological response for genotype 2.
Alisporivir is a cyclophilin inhibitor with demonstrated in vitro and in vivo activity against hepatitis C 11 virus (HCV). We estimated antiviral effectiveness of alisporivir alone or in combination with 12 pegylated-Inteferon (peg-IFN) in 88 patients infected with different HCV genotypes treated for four 13 weeks. The pharmacokinetics of both drugs were modeled and used as driving functions for the viral 14 kinetic model. Genotype was found to significantly affect pegylated-Inteferon effectiveness ($\epsilon$= 86.3% 15 and 99.1% in genotype-1/4 and genotype-2/3, respectively, p\textless{}10 -7) and infected cells loss rate ($\delta$= 16 0.22 vs 0.39 day -1 in genotype-1/4 and genotype-2/3, respectively, p\textless{}10 -6). Alisporivir effectiveness 17 was not significantly different across genotype and was high for doses $\ge$600 mg QD. We simulated 18 virologic responses with other alisporivir dosing regimens in HCV genotype-2/3 patients using the 19 model. Our predictions consistently matched the observed responses, demonstrating that this model 20 could be a useful tool for anticipating virologic response and optimize alisporivir-based therapies.
We used the model for end-stage liver disease (MELD) scoring system to predict the 3-month prognosis of patients with acute-on-chronic liver failure (ACLF) after plasma exchange (PE) and lamivudine treatment, and studied the predictive factors on the prognosis of patients.A total of 280 patients treated with lamivudine were randomly divided into PE and control groups. The relationship between mortality and influential factors of patients was studied by univariate and multivariate analysis.The mortality (49.4%) of patients in the PE group with a MELD score from 30 to 40 was lower than that (86.1%) of the control group (chi(2) = 24.546, P < 0.01). The total bilirubin (TBIL) rebound rate of the dead group was significantly higher than that of the survival group (P < 0.01). Univariate analysis showed that mortality was significantly related to age (P = 0.003), treatment method (P = 0.000), TBIL (P = 0.010), MELD score (P = 0.001), international normalised ratio (P = 0.014), pretreatment HBV-DNA load (P = 0.000), decline of hepatitis B virus (HBV)-DNA load during therapy (P = 0.013), encephalopathy (P = 0.019), and hepatorenal syndrome (P = 0.026). In multivariate analysis, MELD scores of 30-40, treatment method (P = 0.003), pretreatment HBV-DNA load (P = 0.009), decline of HBV-DNA load during therapy (P = 0.016), and encephalopathy (P = 0.015) were independent predictors of mortality; for MELD scores above 40, only the MELD score (P = 0.012) was an independent predictive.PE significantly decreased the mortality of patients with a MELD score of 30-40. For ACLF patients with a MELD score of 30-40, a low viral load pretreatment and quick decline of HBV-DNA load are good predictors for the survival with PE and lamivudine treatment.
Insulin resistance (IR) affects sustained virological response (SVR) in chronic hepatitis C (CHC). The aim of this study was to investigate the effect of adding metformin to peginterferon alfa-2a and ribavirin on the efficacy in patients with genotype 1 CHC and IR.Ninety-eight patients with genotype 1 CHC and IR were randomized into the treatment group (n=49) and the control group (n=49). Patients in the control group received peginterferon alfa-2a and ribavirin, and patients in the treatment group received metformin in addition to peginterferon alfa-2a and ribavirin. The rate of virological response, changes in the homeostasis model assessment of insulin resistance (HOMA-IR) index, and the incidence of side effects were compared between the two groups. Factors influencing the SVR were studied by multivariate analysis.The SVR rate of the treatment group was significantly higher than that of the control group (59.2%, 29/49 vs. 38.8%, 19/49; Chi-square=4.083, p=0.043). The HOMA-IR index of patients in the treatment group was lower than that of patients in the control group at weeks 12, 24, and 48 of the treatment period, and at week 24 of follow-up (3.00±0.65 vs. 3.50±0.72, 1.90±0.45 vs. 2.90±0.64, 1.75±0.40 vs. 2.74±0.48, and 1.60±0.35 vs. 2.60±0.55, respectively; t=3.610, 8.947, 11.091, and 10.738, respectively; p<0.01). Diarrhea was more often seen in the treatment group (28.6%, 14/49 vs. 10.2%, 5/49; Chi-square=5.288, p=0.021). In the multivariate logistic regression analysis, the independent factors associated with SVR were treatment method (p=0.009) and HOMA-IR <2 at week 24 (p=0.011).A combination of metformin, peginterferon alfa-2a, and ribavirin improved insulin sensitivity and increased the SVR rate of patients with hepatitis C genotype 1 and IR, with a good safety profile.
Fulminant hepatitis B is a clinical syndrome that results from massive necrosis of liver cells leading to the development of hepatic encephalopathy. The aim of this study was to evaluate the efficacy of lamivudine in patients with fulminant hepatitis B and study the prognostic factors.A matched retrospective cohort study using data on fulminant hepatitis B patients derived from our hospital database was conducted. Forty patients receiving lamivudine treatment were selected into the lamivudine treatment group with another 40 without lamivudine treatment studied as control. They were matched for sex, age and HBeAg status with lamivudine treatment group. The mortality of patients in two groups was compared. The influential factors on the mortality were studied by Cox proportional hazards model.The mortality of patients in the lamivudine group (n=38) was significantly lower than that of the control group (n=39) (63.2 vs. 84.6%; χ(2) =4.609, P=0.032). For patients without systemic inflammatory response syndrome (SIRS), the mortality of patients in the lamivudine group (n=25) was significantly lower than that of the control group (n=26) (52.0 vs. 80.8%; χ(2) =4.747, P=0.029). In multivariate Cox proportional hazards analyses, for patients without SIRS, age (P=0.037), ratio of total to direct bilirubin (P=0.008), treatment method (P=0.005) and the decline of hepatitis B virus (HBV) DNA load during therapy (P=0.019) were independent predictors of prognosis.Treatment with lamivudine significantly decreases the mortality of fulminant hepatitis B patients without SIRS, and a rapid decline of HBV DNA load is one of the good predictors for the treatment outcome.
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