Hepatitis C virus cure with direct acting antivirals: Clinical, economic, societal and patient value for China.

About 10 million people in China are infected with hepatitis C virus (HCV), with the seroprevalence of anti-HCV in the general population estimated at 0.6%. Delaying effective treatment of chronic hepatitis C (CHC) is associated with liver disease progression, cirrhosis, hepatocellular carcinoma, and liver-related mortality. The extrahepatic manifestations of CHC further add to the disease burden of patients. Managing CHC-related advanced liver diseases and systemic manifestations are costly for both the healthcare system and society. Loss of work productivity due to reduced well-being and quality of life in CHC patients further compounds the economic burden of the disease. Traditionally, pegylated-interferon plus ribavirin (PR) was the standard of care. However, a substantial number of patients are ineligible for PR treatment, and only 40%-75% achieved sustained virologic response. Furthermore, PR is associated with impairment of patient-reported outcomes (PROs), high rates of adverse events, and poor adherence. With the advent of direct acting antivirals (DAAs), the treatment of CHC patients has been revolutionized. DAAs have broader eligible patient populations, higher efficacy, better PRO profiles, fewer adverse events, and better adherence rates, thereby making it possible to cure a large proportion of all CHC patients. This article aims to provide a comprehensive evaluation on the value of effective, curative hepatitis C treatment from the clinical, economic, societal, and patient experience perspectives, with a focus on recent data from China, supplemented with other Asian and international experiences where China data are not available.

Impaired Right Ventricular Mechanics at Rest and During Exercise Are Associated With Exercise Capacity in Patients With Hypertrophic Cardiomyopathy.

Background Impaired right ventricular ( RV ) function indicates RV involvement in patients with hypertrophic cardiomyopathy ( HCM ). We aimed to assess RV function at rest and during exercise in HCM patients and to examine the association between impaired RV mechanics and exercise capacity. Methods and Results A total of 76 HCM patients (48 without and 28 with RV hypertrophy) and 30 age- and sex-matched controls were prospectively recruited. RV function was evaluated at rest and during semisupine bicycle exercise by conventional echocardiography and 2-dimensional speckle-tracking imaging. Exercise capacity was measured by metabolic equivalents. RV functional reserve was calculated as the difference of functional parameters between peak exercise and rest. Compared with controls, HCM patients had significantly higher RV free wall thickness, lower RV global longitudinal strain and RV free wall longitudinal strain at rest and during exercise, and reduced RV systolic functional reserve. Compared with those with HCM without RV hypertrophy, patients with HCM with RV hypertrophy had lower metabolic equivalents. Among HCM patients, an effective correlation was seen between exercise capacity and peak exercise RV global longitudinal strain and peak exercise RV free wall longitudinal strain. A binary logistic regression model revealed several independent predictors of exercise intolerance in HCM patients, but receiver operating characteristic curve analysis indicated exercise RV global longitudinal strain had the highest area under the curve for the prediction of exercise intolerance in HCM patients. Conclusions HCM patients have RV dysfunction and reduced contractile reserve. Exercise RV global longitudinal strain correlates with exercise capacity and can independently predict exercise intolerance. In addition, patients with HCM with RV hypertrophy exhibit more reduced exercise capacity, suggesting more severe disease and poorer prognosis.

Influence of impaired right ventricular contractile reserve on exercise capacity in patients with precapillary pulmonary hypertension: A study with exercise stress echocardiography.

OBJECTIVES: Right ventricular (RV) contractile reserve reflects the ability of RV to accommodate the increased afterload and may play an essential role in the evaluation of precapillary pulmonary hypertension (PH). This study aimed to assess RV contractile reserve based on exercise stress echocardiography (ESE) and to determine the echocardiographic determinants of exercise capacity in patients with precapillary PH. METHODS: A total of 31 patients with precapillary PH and 15 age- and sex-matched healthy control subjects were prospectively recruited. All subjects underwent ESE to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. Patients with precapillary PH also underwent cardiopulmonary exercise test (CPET), and data pertaining to peak oxygen uptake (peak VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) were collected. RESULTS: Right ventricular contractile reserve including change in tricuspid annular plane systolic excursion (∆TAPSE), change in RV fractional area change (∆RVFAC), and change in Doppler-derived tricuspid lateral annular peak systolic velocity (∆S') was significantly depressed in precapillary PH patients compared with control subjects (P < 0.05). Parameters of RV function and RV contractile reserve were markedly associated with maximal exercise capacity (P < 0.05). ∆RVFAC was an independent predictor of peak VO2 (r2  = 0.601, P < 0.05). CONCLUSIONS: Assessment of RV contractile reserve facilitates identification of subclinical dysfunction and evaluation of clinical status and severity of precapillary PH. ESE as a noninvasive method may provide a comprehensive clinical assessment and facilitate therapeutic decision-making for these patients.

Decreased biventricular mechanics and functional reserve in nonobstructive hypertrophic cardiomyopathy patients: implications for exercise capacity.

The present study investigated the changes of biventricular mechanics at rest and during exercise and examined the association between exercise capacity and biventricular mechanics and functional reserve in nonobstructive hypertrophic cardiomyopathy (NHCM) patients. A total of 50 NHCM patients and 25 controls were consecutively recruited for this study. Using echocardiography and two-dimensional speckle-tracking imaging, an experienced echocardiographer determined the following indices: RV free wall longitudinal strain (RVFWLS), LV global longitudinal strain (LVGLS), strain rate (SR), and functional reserve of strain values. We also investigated the relationships between biventricular mechanics and exercise capacity using metabolic equivalents (METs). NHCM patients had lower RVFWLS, LVGLS, systolic SR, early diastolic SR, and systolic and diastolic reserve during exercise compared to controls. An association of biventricular mechanics (LVGLS, RVFWLS) with exercise capacity at rest and during exercise was established. Multivariable logistic regression revealed that RVFWLS and LVE/e' during exercise (RVFWLS-exe, E/e'-exe) were independent predictors of exercise intolerance. Receiver operating characteristic curve analysis indicated that LVE/e'-exe had a higher area under the curve for predicting exercise intolerance in NHCM patients. In hierarchical analysis, RVFWLS-exe provided an incremental predictive value of exercise intolerance over LVGLS during exercise (LVGLS-exe) and LVE/e'-exe. LVE/e'-exe also changed incrementally compared to LVGLS-exe and RVFWLS-exe. NHCM patients have decreased biventricular mechanics at rest and during exercise and impaired biventricular functional reserve, and biventricular mechanics are associated with functional capacity. We propose that simultaneous evaluation of biventricular function should provide incremental predictive value for exercise intolerance.

Impaired left ventricular mechanics and functional reserve are associated with reduced exercise capacity in patients with hypertrophic cardiomyopathy.

BACKGROUND: Reduced metabolic equivalents (METs) are an indicator of exercise intolerance, which predicts poor prognosis in hypertrophic cardiomyopathy (HCM) patients. We sought to evaluate the changes in left ventricular (LV) mechanics and functional reserves, as well as their association with functional capacity in HCM patients. METHODS: Seventy HCM patients and thirty controls were included in this study. LV mechanics were evaluated at rest and during exercise by echocardiography and two-dimensional speckle-tracking imaging to obtain parameters of functional reserve, LV global longitudinal strain (LVGLS), strain rate (SR), and circumferential strain. RESULTS: Hypertrophic cardiomyopathy (HCM) patients had lower LVGLS, systolic SR, early and late diastolic SR at rest and during exercise, and reduced absolute and relative systolic and diastolic reserve compared to controls. LV circumferential strain was significantly higher at rest but lower during exercise in HCM patients. Exercise capacity was markedly reduced in HCM patients, and peak exercise LVGLS (LVGLS-exe) significantly correlated with exercise capacity. Multivariate regression analyses showed that LVGLS-exe, LV filling pressure during exercise (E/e'-exe), and LV mass index (LVMI) were independent predictors of exercise capacity. Moreover, LVGLS-exe displayed incremental predictive value over E/e'-exe and LVMI for exercise intolerance. Receiver operating characteristic curve analysis showed LVGLS-exe had optimal accuracy for predicting exercise intolerance in HCM patients. CONCLUSIONS: Hypertrophic cardiomyopathy (HCM) patients have reduced LV mechanics at rest and during exercise and impaired mechanical reserve. LVGLS-exe is associated with exercise capacity and is an optimal predictive value for reduced exercise capacity in HCM patients.

A Simplified Ultrasound Comet Tail Grading Scoring to Assess Pulmonary Congestion in Patients with Heart Failure.

Ultrasound lung comets (ULCs) are a nonionizing bedside approach to assess extravascular lung water. We evaluated a protocol for grading ULC score to estimate pulmonary congestion in heart failure patients and investigated clinical and echocardiographic correlates of the ULC score. Ninety-three patients with congestive heart failure, admitted to the emergency department, underwent pulmonary ultrasound and echocardiography. A ULC score was obtained by summing the ULC scores of 7 zones of anterolateral chest scans. The results of ULC score were compared with echocardiographic results, the New York Heart Association (NYHA) functional classification, radiologic score, and N-terminal pro-b-type natriuretic peptide (NT-proBNP). Positive linear correlations were found between the 7-zone ULC score and the following: E/e', systolic pulmonary artery pressure, severity of mitral regurgitation, left ventricular global longitudinal strain, NYHA functional classification, radiologic score, and NT-proBNP. However, there was no significant correlation between ULC score and left ventricular ejection fraction, left ventricle diameter, left ventricular volume, or left atrial volume. A multivariate analysis identified the E/e', systolic pulmonary artery pressure, and radiologic score as the only independent variables associated with ULC score increase. The simplified 7-zone ULC score is a rapid and noninvasive method to assess lung congestion. Diastolic rather than systolic performance may be the most important determinant of the degree of lung congestion in patients with heart failure.

Integrative Cardiopulmonary Ultrasound for Interstitial Lung Disease Assessment: Correlation between Lung Ultrasound Performance and Cardiac Involvement.

The aims of this study were to apply integrative cardiopulmonary ultrasound (thoracic ultrasound) to the evaluation of patients with interstitial lung disease (ILD) and to determine the relationship between lung ultrasound signs and echocardiographic parameters such as systolic pulmonary artery pressure (SPAP) and various right ventricular parameters. ILD patients and healthy controls underwent lung ultrasound (LUS) and echocardiographic tests. In addition to traditional echocardiographic parameters, right ventricular free wall longitudinal strain (RVLS_FW) was measured using 2-D speckle-tracking echocardiography. The degree of pulmonary fibrosis or the disease severity of each ILD patient was scored with a semiquantitative scoring method, taking into account multiple LUS signs. Statistical analyses were performed to compare various parameters between ILD patients with and those without pulmonary hypertension. Correlations between the different parameters were then evaluated, and the LUS scores were used to predict pulmonary hypertension using a receiver operating characteristic curve analysis. Among the 90 patients who qualified for entry into this study, 30% (n = 27) had pulmonary hypertension. The patients with pulmonary hypertension had larger right ventricular dimensions, lower RVLS_FW and higher LUS scores. An effective correlation was found between ILD LUS scores and echocardiographic parameters, especially SPAP (r = 0.735, p < 0.001). The groups were comparable with respect to most echocardiographic parameters, with mild, moderate and severe pulmonary fibrosis, whereas SPAP was significantly higher in the moderate and severe groups. RVLS_FW was obviously reduced in the group with severe pulmonary fibrosis. Although RVLS_FW in the mild pulmonary fibrosis group was in the normal range, it was slightly reduced compared with that of the controls. A cutoff of more than 16 LUS points had 85.2% sensitivity and 80.3% specificity in predicting elevated SPAP (>36 mm Hg). Thoracic ultrasound is useful in the assessment of ILD. As ILD progresses, the structure or function of the right ventricle gradually deteriorates. LUS not only detects lung conditions in ILD, but also indirectly reflects SPAP and right ventricular function. Integrated use of LUS and echocardiography will provide an invaluable point-of-care imaging modality to facilitate the diagnosis, management and treatment of patients with ILD.

High-Resolution Transthoracic Ultrasonography for Assessment of Pleural Lines in Patients With Dyspnea With CT Comparison: An Observational Study.

OBJECTIVES: Detection of B-line in dyspneic patients is often accompanied by abnormal changes of pleural line on transthoracic ultrasonography (TUS). The aim of the study was to evaluate the relevance and diagnostic performance of pleural line abnormalities and B-lines detected on high-resolution TUS against the computed tomography (CT) findings. METHODS: Transthoracic ultrasonography was performed in patients admitted to the emergency department with dyspnea. The pleural line and accompanying B-line were assessed using a linear transducer. The TUS findings were assessed against the corresponding high-resolution CT findings in the same location, which were considered to be the gold standard. RESULTS: Out of a total of 116 patients, 68.1% had changes of the pleural line on TUS. The characteristic changes of the pleural line were classified into four types: slightly rough pleural line with confluent B-lines on TUS corresponded with CT findings of ground-glass opacity; irregular and interrupted pleural line with confluent B-lines corresponded with parenchymal infiltration; fringed pleural line with confluent B-lines corresponded with superimposed ground-glass and irregular reticular opacities; and fringed pleural line with scattered B-lines corresponded with irregularly thickened interlobular septa. Wavy pleural line indicated subpleural emphysema. The coexistence of more than one abnormal pleural line was also found in 31 cases (26.7%). CONCLUSIONS: High-resolution TUS may help in the initial assessment of lung pathology by its ability to identify pleural line abnormalities and B-lines that are shown to be associated with CT, which could add diagnostic value in the emergency evaluation of dyspneic patients.

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients.

AIM: To investigate the efficacy of switching to pegylated interferon-α-2a (PegIFNα-2a) treatment in nucleos(t)ide analog (NA)-treated chronic hepatitis B (CHB) responder patients. METHODS: A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir (ETV) for at least 48 wk and had serum hepatitis B virus (HBV)-DNA < 500 IU/mL, serum hepatitis B envelope antigen (HBeAg) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to PegIFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the PegIFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS: After 48 wk of therapy, the decrease in hepatitis B surface antigen (HBsAg) levels was greater in the PegIFNα-2a group than in the ETV group (3.1340 log10 IU/mL vs 3.6950 log10 IU/mL, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBsAg loss when switched to PegIFNα-2a (15.91% vs 0%, P = 0.018). The HBeAg serological conversion rate was higher in the PegIFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes (34.38% vs 21.88%, P = 0.232). In the PegIFNα-2a group, patients with HBsAg levels < 1500 IU/mL at baseline had higher HBeAg seroconversion and HBsAg loss rates at week 48 than those with HBsAg levels ≥ 1500 IU/mL (HBeAg seroconversion: 17.86% vs 62.5%, P = 0.007; HBsAg loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBsAg levels < 1500 IU/mL at week 24 had higher HBsAg loss rates after therapy than those with HBsAg levels ≥ 1500 IU/mL (36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBeAg seroconversion rates (47.06% vs 25.93%, P = 0.266). CONCLUSION: NA-treated CHB patients switched to sequential PegIFNα-2a achieved highly potent treatment termination safely.

In vitro characterization and inhibition of the interaction between ciprofloxacin and berberine against multidrug-resistant Klebsiella pneumoniae.

Ciprofloxacin is a quinolone antibiotic used to treat Klebsiella pneumoniae infections in the clinic. Previous studies have demonstrated that berberine exhibits antibacterial activity and less acquired resistance related to efflux pumps. The multidrug efflux pump acrAB-tolC can be stimulated to expel as much toxic material as possible from the cells, but a detrimental effect can be produced owing to an overcrowded periplasm with excess expression products, which inhibits bacterial growth. In this study, the in vitro antibacterial activities of ciprofloxacin in combination with berberine were evaluated and compared with those of ciprofloxacin and berberine alone by evaluating the MIC, MBC and summation fractional IC against 20 clinical multidrug-resistant K. pneumoniae isolates, 1 quality control bacterium and 1 induced-resistance bacterium. Susceptibility tests showed that the MIC for the combination of berberine and ciprofloxacin was 1/2 that of the individual agents or less. Antimicrobial activities of 18.18% synergy and 77.27% additivity were found. Furthermore, synergism was verified through a time-kill assay, which suggested that the synergistic antibacterial effect of the two-drug combination may, to some extent, be related to the high expression of the acrAB-tolC and acrR multidrug efflux pumps. Indeed, the expression of these genes was increased >14-fold in the isolates affected by ciprofloxacin-berberine combination synergism.

Vitamin D Level is Associated with Increased Left Ventricular Mass and Arterial Stiffness in Older Patients with Impaired Renal Function.

BACKGROUND Impaired renal function is common among older patients. Deficiency of vitamin D is a frequent phenomenon among patients with impaired renal function, who are likely to develop cardiovascular diseases. This study aimed to explore the association of 25 (OH) D levels with left ventricular mass and arterial stiffness in older patients with impaired renal function. MATERIAL AND METHODS Based on their admission estimate glomerular filtration rate (eGFR), 273 inpatients (≥65 years) were allocated into a normal eGFR group (≥60 ml/min) and an impaired eGFR group (<60 ml/min). The 25 (OH) D levels were measured and the left ventricular mass index (LVMI) was estimated. Pulse wave velocity (PWV) was used to explore arterial stiffness. RESULTS The 25 (OH) D levels of patients in the impaired eGFR group were significantly lower than in the normal eGFR group [(11.92±6.01) µg/L vs. (18.14±8.07) µg/L, p<0.05). LVMI and PWV were both significantly higher in the impaired eGFR group than in the normal eGFR group [(104.89±33.50) g/m2 vs. (92.95±18.95) g/m2, P<0.05; (15.99±3.10) m/s vs. (13.62±2.90) m/s, P<0.05]. After adjusting for age, sex, eGFR, cardiovascular risk factors, serum calcium, and iPTH levels, the inverse association between LVMI and 25 (OH) D, PWV, and 25 (OH) D were statistically significant. CONCLUSIONS Vitamin D level is lower in older patients with impaired renal function. Lower vitamin D levels were correlated with higher left ventricular mass and increased arterial stiffness in older patients.

Effects of entecavir and lamivudine for hepatitis B decompensated cirrhosis: meta-analysis.

AIM: To compare the effects of entecavir (ETV) and lamivudine (LAM) for the treatment of hepatitis B decompensated cirrhosis using a meta-analysis. METHODS: We conducted a literature search for all eligible studies published prior to May 30, 2013 using PUBMED, MEDLINE, EMBASE, the China National Knowledge Infrastructure (CNKI), the VIP database, the Wanfang database and the Cochrane Controlled Trial Register. Randomized controlled trials (RCTs) comparing ETV with LAM for the treatment of hepatitis B decompensated cirrhosis were included. The data were analyzed with Review Manager Software 5.0.2. We used RR as an effect measure, and reported its 95%CI. The meta-analysis was performed using either a fixed-effect or random-effect model, based on the absence or presence of significant heterogeneity. Two reviewers assessed the risk of bias and extracted data independently and in duplicate. The analysis was executed using the main outcome parameters including hepatitis B virus (HBV) DNA undetectability, HBV DNA level, hepatitis B e antigen (HBeAg) seroconversion, alanine aminotransferase (ALT) level, albumin level, total bilirubin (TBIL) level, prothrombin time activity (PTA) level, Child-Turcotte-Pugh (CTP) score, mortality, drug-resistance, and adverse reactions. Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics and the therapeutic effects of the two agents. RESULTS: Thirteen eligible trials (873 patients in total) were included and evaluated for methodological quality and heterogeneity. Of these studies, all had baseline comparability, 12 of them reported baseline values of the two treatment groups in detail. Following various treatment durations (12, 24, 36, 48 and > 48 wk), both ETV and LAM significantly reduced HBV DNA level, however, reductions were greater in the ETV group (MD = -0.66, 95%CI: -0.83-0.50, P < 0.00001), (MD = -0.93, 95%CI: -1.36-0.51, P < 0.0001), (MD = -1.4, 95%CI: -1.78-1.01, P < 0.00001), (MD = -1.18, 95%CI: -1.90-0.46, P = 0.001), (MD = -0.14, 95%CI: -0.17-0.11, P < 0.00001, respectively). At 12, 24 and 48 wk of treatment, ETV had a significant effect on the rate of HBV DNA undetectability (RR = 1.55, 95%CI: 1.22-1.99, P = 0.0004), (RR = 1.25, 95%CI: 1.13-1.38, P < 0.0001), (RR = 1.2, 95%CI: 1.10-1.32, P < 0.0001, respectively). Although HBeAg seroconversion in the ETV group was more pronounced than that in the LAM group at 24 wk (27.90% vs 26.19%) and 48 wk (31.52% vs 25.00%) of treatment, there was no statistically significant difference between them (RR = 1.49, 95%CI: 0.98-2.28, P = 0.07), (RR = 1.27, 95%CI: 0.98-1.65, P = 0.07, respectively). Following various treatment durations, both the ETV group and the LAM group showed significantly improved liver function (ALT, AIB, TBIL, PTA and CTP levels) and reduced mortality (ETV 6.37%, LAM 7.89%). The effects in the ETV group (0.33%) were statistically lower than those in the LAM group (14.33%) regarding the rate of drug-resistance (RR = 0.1, 95%CI: 0.04-0.24, P ≤ 0.00001). In addition, no severe adverse reactions were observed in the two treatment groups. CONCLUSION: ETV and LAM significantly improved liver function and reduced mortality. Both drugs produced similar serological responses, and were safe and well tolerated. However, ETV resulted in a better virological response and lower drug-resistance, but is more expensive.

Effects of telbivudine and entecavir for HBeAg-positive chronic hepatitis B: a meta-analysis.

AIM: To compare the effects of telbivudine (LDT) and entecavir (ETV) in treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B by meta-analysis. METHODS: We conducted a literature search using PubMed, MEDLINE, EMBASE, the China National Knowledge Infrastructure, the VIP database, the Wanfang database and the Cochrane Controlled Trial Register for all relevant articles published before April 1, 2012. Randomized controlled trials (RCTs) comparing LDT with ETV for treatment of HBeAg-positive chronic hepatitis B were included. The data was analyzed with Review Manager Software 5.0. We used relative risk (RR) as an effect measure, and reported its 95% CI. Meta-analysis was performed using either a fixed-effect or random-effect model, based on the absence or presence of significant heterogeneity. Two reviewers assessed the risk of bias and extracted data independently and in duplicate. The analysis was executed using the main outcome parameters including hepatitis B virus (HBV) DNA undetectability, alanine aminotransferase (ALT) normalization, HBeAg loss, HBeAg seroconversion, drug-resistance, and adverse reactions. Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics with the therapeutic effects of the two agents. RESULTS: Thirteen eligible trials (3925 patients in total) were included and evaluated for methodological quality and heterogeneity. In various treatment durations of 4 wk, 8 wk, 12 wk, 24 wk, 36 wk, 48 wk, 52 wk, 60 wk and 72 wk, the rates of HBV DNA undetectability and ALT normalization in the two groups were similar, without statistical significance. At 4 wk and 8 wk of the treatment, no statistical differences were found in the rate of HBeAg loss between the two groups, while the rate in the LDT group was higher than in the ETV group at 12 wk, 24 wk, 48 wk and 52 wk, respectively (RR 2.28, 95% CI 1.16, 7.03, P = 0.02; RR 1.45, 95% CI 1.16, 1.82, P = 0.001; RR 1.45, 95% CI 1.11, 1.89, P = 0.006; and RR 1.86, 95% CI 1.04, 3.32, P = 0.04). At 4 wk, 8 wk, 60 wk and 72 wk of the treatment, there were no significant differences in the rate of HBeAg seroconversion between the two groups, while at 12 wk, 24 wk, 48 wk and 52 wk, the rate in the LDT group was higher than in the ETV group (RR 2.10, 95% CI 1.36, 3.24, P = 0.0008; RR 1.71, 95% CI 1.29, 2.28, P = 0.0002; RR 1.86, 95% CI 1.36, 2.54, P < 0.0001; and RR 1.87, 95% CI 1.21, 2.90, P = 0.005). The rate of drug-resistance was higher in the LDT group than in the ETV group (RR 3.76, 95% CI 1.28, 11.01, P = 0.02). In addition, no severe adverse drug reactions were observed in the two groups. And the rate of increased creatine kinase in the LDT group was higher than in the ETV group (RR 5.58, 95% CI 2.22, 13.98, P = 0.0002). CONCLUSION: LDT and ETV have similar virological and biomedical responses, and both are safe and well tolerated. However, LDT has better serological response and higher drug-resistance.

[Relationship between the genetic polymorphism of CYP3A5 gene and the clinical response to bicyclol in chronic hepatitis B].

OBJECTIVE: To investigate the relationship between the genetic polymorphisms of CYP3A5 and the clinical effectiveness of Bicyclol on patients with chronic hepatitis B to make individual medication possible. METHODS: 34 cases of chronic hepatitis B were treated by bicyclol tablets for 24 weeks. Liver function indexes (ALT and AST) were determined before and after treatment. Blood CYP3A5 genotyping of each patient was determined by the PCR-RFLP analysis. RESULTS: All subjects were genotyped for the CYP3A5*3 gene and divided into different group. The groups comprised subjects with CYP3A5*3 carriers (n=18) and CYP3A5*1 carriers (n=16) which include CYP3A5*1/*1 (n=2) and CYP3A5*1/*3 (n=14). Compared with pre-treatment, the serum ALT and AST levels were decreased obviously in all patients. The mean percentage reduction of serum ALT and AST levels were significantly greater in subjects with CYP3A5*3 carriers (79.73% and 74.76%) than in those with CYP3A5*1 carriers (65.90% and 49.63%; P < 0.05) The recovery rates of ALT and AST were significantly highter in CYP3A5*3 carriers than those in CYP3A5*1 carriers (P < 0.05). CONCLUSION: CYP3A5 genotype has an impact on the therapeutic effects of Bicyclol. The subjects with CYP3A5*3 carriers is more effective than the subjects with CYP3A5*1 carriers. CYP3A5 genotyping may be helpful in predicting therapeutic effects of Bicyclol especially in the terms of decreasing ALT and AST.

[Clinical observation of liver damages in epidemic hemorrhagic fever].

OBJECTIVE: To study the changes in liver function in patients with epidemic hemorrhagic fever (EHF). METHOD: A retrospective analysis of the laboratory tests of liver function in 103 patients with EHF and control subjects was carried out. RESULTS: The alanine aminotransferase (ALT), serum bilirubin (SB) and albumin levels in patients with severe and critical liver damages significantly differed from those in milder cases, and more sever liver damages were found in the death cases of EHF than in survived patients in terms of ALT and SB increment (P=0.000). The liver damage was related to the clinical type, age and the levels of blood platelet , albumin, lactic dehydrogenase and creatinine in EHF cases (P=0.000, 0.000, 0.030, 0.010, 0.000 and 0.013, respectively). CONCLUSIONS: Liver damage is common in patients with EHF and exacerbates with the severity of the disease. Monitoring of ALT, SB and albumin is helpful for evaluating the progression and prognosis of EHF.