Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin in autoantibody-positive chronic hepatitis C patients / 中华肝脏病杂志

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.

Lamivudine-resistant analysis and management for chronic hepatitis B patients with initial lamivudine therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the factors influencing the long-term usage of lamivudine (LAM) in chronic hepatitis B (CHB) patients and the management after drug-resistance.</p><p><b>METHODS</b>383 cases of naive CHB patients in our outpatient clinic were treated with lamivudine (100 mg/d) and followed up for at least over 1 year from 2001 to 2010. 129 cases encountered lamivudine-resistance and were then divided into two groups: patients in group A were switched to adefovir dipivoxil (ADV) alternative treatment and those patients in group B were added with ADV for continuous treatment. Efficacy assessment factors included serum HBV markers, HBV DNA, ALT, AFP and other biochemical indicators.</p><p><b>RESULTS</b>Among the 383 cases, patients with HBV DNA negative conversion (PCR below test line) at 3 months, 6 months, 1 year, 2 years, 3 years and > 3 years after initial treatment were respectively 156 cases (40.7%), 213 cases (55.6%), 228 cases (59.5% ), 217cases (56.7%), 214 cases (55.9%) and 213 cases (55.6%). HBeAg/HBeAb seroconversion occurred in 62 cases (22.6%). 12 cases were found with primary LAM resistance, 129 cases with HBV breakthrough and rebound, the cumulative resistance rate was 36.8% and the cumulative rebound rate was 34.8%. High baseline viral load, baseline ALT levels < 2 ULN, Lower virologic response rate at week 24 were associated with a higher rebound rate (chi2 is 35.716, 8.728, 43.534, respectively, all with P < 0.01).Viral breakthrough and rebound occurred in 112 patients (86.8%) within 1 year and a half, 123 patients (95.3%) occurred at the end of 2 years and no patient with viral breakthrough and rebound after 5 years. For the patients with viral rebound in group A and group B, the rates of HBV DNA loss were 22.7% (15/66) and 58.7% (37/63) respectively, and the viral response rates were 59.1% (39/66) and 87.3% (52/63) respectively, with chi2 values equaled 17.364 and 12.975 respectively (P < 0.01).</p><p><b>CONCLUSION</b>For the chronic hepatitis B patients on initial treatment with lamivudine, the viral rebound occurred mainly within 2 years. LAM combined with ADV is more effective than ADV alone for lamivudine-resistant patients.</p>

Association between the influential factors and the effectiveness of pegylated interferon alpha-2a plus ribavirin as a combination treatment for chronic hepatitis C patients / 中华肝脏病杂志

To evaluate the efficacy and to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2a (PegIFN alpha-2a) plus ribavirin (RBV) and the effectiveness of antiviral therapy. We analyzed data from 117 patients treated for 48 weeks with PEG-IFN alpha-2a (135mug or 180mug/week) plus weight-based RBV (800 mg/d for patients is less than or equal to 65 kg, 1000 mg/d for patients 65-75 kg and 1200 mg/d for patients is more than or equal to 75 kg) under care at West China Hospital. HCV RNA was assessed at baseline, Week 4, 12 and 24, the end of treatment (EOT) and after 24 weeks follow-up (sustained virological response; SVR) with a test range of 1.0*10(3) to 5.0*10(7) IU/ml. Patients were stratified by age, gender, weight, route of transmission, duration of infection, baseline HCV RNA level and PegIFN alpha-2a or RBV dosage. HCV genotype was assessed in 29 patients (genotype 1b, 21; genotype 2a, 7; genotype 1b/2a, 1). Rapid virological response (RVR; HCV RNA negative at week 4), complete early virological response (cEVR; HCV RNA negative at week 12), EOT response, and SVR were achieved in 88 (75.2%), 110 (94%), 114 (97.4%) and 96 (82.1%) patients, respectively. Younger age, lower weight and shorter speculated infection years were associated with higher SVR rates (91.4% vs 72.9%, x2=6.796, P value is less than 0.05; 85% vs 50%, x2=5.433, P value is less than 0.05; 96.7% vs 77%, x2=5.852, P value is less than 0.05). SVR significantly increased with treatment length (38.5%, 66.7%, and 88.8% for is less than or equal to 29 weeks, 29-38 weeks, and is more than or equal to 38 weeks, respectively). SVR significantly increased with total cumulative treatment doses (38.5%, 66.7% and 88.8% for is less than or equal to 60%, 60%-80% and is more than or equal to 80% of PegIFN dose respectively; 33.3%, 85.3% and 96.8% for is less than or equal to 60%, 60%-80% and is more than or equal to 80% in RBV dose respectively) in all patients. Less than 80% of standard dose of RBV was not sufficient even if given enough PegIFN (is more than or equal to 80% cumulative treatment dose) in patients who achieved RVR. Chinese patients treated with peginterferon alpha-2a plus ribavirin have high rates of SVR. It is important to complete the target length of treatment and to continue the target dosage to achieve SVR.

Factors Predicting the Efficacy of Adefovir Dipivoxil on Treatment-Naive Chronic Hepatitis B Patients at 48 Weeks

BACKGROUND/AIMS: To reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV. METHODS: In total, 168 treatment-naive CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values. RESULTS: Multiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p or =10(3) copies/mL at week 24 is observed.

Assessment of disease activity and liver fibrosis in chronic viral hepatitis by magnetic resonance diffusion-weighted imaging / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) technique in assessing the disease activity and liver fibrosis of chronic viral hepatitis.</p><p><b>METHODS</b>A total of 49 patients with chronic viral hepatitis who received liver biopsy and 10 healthy volunteers were included in this study. All of them underwent DWI on a 3.0 T magnetic resonance imaging system. When the gradient factor b value was set at 100, 200, 400, 600, and 800 s/mm2, the apparent diffusion coefficient (ADC) of the liver was measured respectively. Biopsy specimens were scored for necroinflammation and liver fibrosis according to the Knodell histological activity index.</p><p><b>RESULTS</b>The ADC values of the right lobe in both controls and patients were lower than those of the left lobe. When the b value was set at 400, 600, and 800 s/mm2, the differences of the ADC values between the fibrosis group (n = 36) and the non-fibrosis group (n = 23, including 10 cases of normal subjects) were statistically significant (P < 0.01). When the b value was set at 800 s/mm2, the ADC values among the different degrees of necroinflammation and grades of liver fibrosis were also significantly different (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>DWI is a valuable method for in vivo and noninvasive assessment of the disease activity and liver fibrosis of chronic viral hepatitis.</p>

Impact of Antimicrobial Agents on Transcription of Gene hld in Forming Process of Staphylococcus epidermidis Biofilm / 中华医院感染学杂志

OBJECTIVE To investigate the transcription level of gene hld of Staphylococcus epidermidis in the biofilm forming and detaching under MIC antibiotic and explore the relationship between biofilm-related drug resistance and persistant infection.METHODS The transcription level of gene hld of S.epidermidis under MIC concentration of 4 antibiotics was compared with those of the control group without antibiotics by SYBR real-time fluorescent quantitative RT-PCR at the different time point of biofilm formation and detachment.RESULTS The transcription of gene hld decreased rapidly from initial adherence,and droped continuously for few hours.There was an increase from 24 hours to 72 hours in groups without antibiotics but not in antibiotics groups,the differenet was significant.CONCLUSIONS Antibiotics improve adherence at first and then prevent matrix decomposition water-conducting tube and detachment of cells by impact of transcription of gene hld,it can protect cells from killing by inhibiting the penetration of biotics and prevent them become planktonic cells after detachment from biofilm.

The relationship between 31P magnetic resonance spectroscopy and the histopathology of livers of chronic viral hepatitis patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the correlations between 31P-magnetic resonance spectroscopy (MRS) findings and histopathological grading and staging of the livers of chronic viral hepatitis patients.</p><p><b>METHODS</b>Thirty-one patients with chronic viral hepatitis and 18 healthy volunteers were enrolled for this study. All of them underwent routine MRI plain scan and 31P-MRS of their livers. Peak areas of PME, PDE, PCr, Pi, gamma-ATP, beta-ATP and alpha-ATP were calculated. The concentrations of the phosphorus compounds of their livers, including PME, PDE, PCr, Pi, gamma-ATP, beta-ATP and alpha-ATP were measured. Percutaneous liver biopsies were performed on all 31 patients 0 to 7 days after their 31P-MRS examinations. Biopsy specimens were scored for fibrosis and necroinflammation according to the Knodell histological activity index. According to their necroinflammation scores, the 31 patients were divided into groups: slight hepatitis (7 patients), mild hepatitis (11), moderate hepatitis (8) and severe hepatitis (5). According to their fibrosis scores, the patients were divided into groups: no fibrosis (7 patients), portal fibrosis (11), bridging fibrosis (5) and cirrhosis (8).</p><p><b>RESULTS</b>The PME%, PDE% and PME/PDE of the hepatitis patients and of the control volunteers had significant statistical differences. The differences of PME%, PDE% and PME/PDE among different grades and stages also had statistical significance. When PME/PDE=0.78, 0.95 and 1.11 were set as the cut-off points for different grades of necroinflammation, and PME/PDE=0.79, 0.95 and 1.10 were set as the cut-off points for different stages of fibrosis, a sensitivity of 80.0%-87.5% and a specificity of 42.9%-72.7% were achieved.</p><p><b>CONCLUSION</b>PME/PDE is a sensitive marker for diagnosing the severity of chronic viral hepatitis. A rise of PME/PDE in hepatitis patients represents an increase of synthesis and a decrease in the breakdown of hepatocytes.</p>