Evaluation of the star family doctors training program: an observational cohort study of a novel continuing medical education program for general practitioners within a compact medical consortium: a quantitative analysis.

INTRODUCTION: To determine the effectiveness of the Star Family Doctors Training Program, a comprehensive Continuing professional development (CPD) program for general practitioners (GPs) in a compact medical consortium. PATIENTS AND METHODS: Observational cohort study with a quantitative analyses in primary health care institutions in Sichuan Province. The interventions were as following: (1) The Star Family Doctors Training Program is a full-time, local government allocation program certified by the Health Department of Sichuan Province, emphasizing small group learning and practice, and using standard patients and medical patient simulators; 30 participants were selected by their institutions. (2) The control group underwent a self-financed after-work CPD program using conventional lectures; 50 participants were self-selected. Short-term effectiveness assessed using immediate post-training tests and self-evaluations; long-term (1 year) effectiveness evaluated using self-reported surveys. RESULTS: The study involved 80 GPs (28.75% men; mean age: 38.2 ± 9.2 years). The average post-training total score was higher in the STAR group than in the control group (72.83 ± 5.73 vs. 68.18 ± 7.64; p = 0.005). Compared to the controls, STAR participants reported seeing more patients (all p < 0.05), and had more patients who signed family-doctor contracts (p = 0.001) as well as increased patient satisfaction (p = 0.03), respectively. STAR-group trainees appraised the program higher and were more willing to recommend it to colleagues (90% vs. 64%, p = 0.011). CONCLUSION: The Star Family Doctors Training Program achieved good responses and provides a reference for future CPD programs.

Plasma miR-30a-5p as an early novel noninvasive diagnostic and prognostic biomarker for lung cancer.

Aim: Circulation miRNAs have become increasingly appreciated in the diagnosis and prognosis of lung cancer. This study aims to identify and evaluate plasma miRNA-30a-5p as an early noninvasive biomarker for the diagnosis and prognosis of lung cancer. Pateints & methods: Expression levels of plasma miRNA 30a-5p were measured by quantitative real-time PCR. Receiver operating characteristic analysis and area under the curve were used to differentiate malignant from benign tumors and from healthy controls. Kaplan-Meier curves and Cox regression were used to determine survival and prognosis. Results: Our results suggest that the level of miRNA-30a-5p in plasma might be a considerable early novel noninvasive diagnostic and prognostic biomarker for lung cancer. Conclusion: Prospective studies must be performed to confirm this new early novel noninvasive diagnostic and prognostic biomarker for lung cancer.

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B.

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.

Mutations in basal core promoter is associated with significant fibrosis in both HBeAg positive and negative treatment-naïve chronic hepatitis B.

AIM: Assessment of liver fibrosis is important for the decision of whether to administrate antiviral treatment in chronic Hepatitis B (CHB) patients. The objective was to investigate the relationship between clinical factors and fibrosis, identify predictors of significant fibrosis in Chinese CHB patients. METHODS: Two hundred and seventy-four treatment-naïve CHB patients (208 HBeAg-positive and 66 HBeAg-negative) who performed transient elastography were consecutively included. We assessed ALT, HBsAg, HBeAg, HBV-DNA, HBV genotype and precore (PC)/basal core promoter (BCP) variants and liver stiffness measurement (LSM) values. RESULTS: One hundred and nine patients (39.78%) had significant fibrosis (F≥2, include those with liver cirrhosis). On univariate analysis, significant fibrosis was associated with older age (P<0.001), high ALT levels (P=0.003), lower HBsAg levels (P<0.001), lower HBV DNA levels (P<0.001), HBeAg negative (P<0.001), presence of BCP (P<0.001) and combined BCP/PC mutations (P=0.001). Multivariate logistic regression analysis showed that the strongest independently associated predictors of significant fibrosis (F≥2) were the presence of HBV BCP mutations (P<0.001) and older age (P<0.001), followed by presence of lower HBsAg (P<0.001), higher ALT levels (P=0.006), PC mutations (P=0.011). The diagnostic accuracy of the combination (age, ALT, HBsAg, BCP/PC variants) model with an area under the receiver-operating characteristic curve of 0.819 (cut-off value was 0.349, P<0.001, 95% CI 0.731-0.914) in predicting significant fibrosis. CONCLUSIONS: We identified four independent risk factors (age, ALT, HBsAg, HBV BCP/PC variants) in predicting significant fibrosis. HBV BCP variants was the strongest predictor of significant fibrosis. The combination of these four variables may facilitate the assessment and management of fibrosis in HBV infected patients.

Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection.

BACKGROUND: The aim of this study was to determine the role of baseline hepatitis B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver inflammation in patients infected with HBV with serum alanine aminotransferase (ALT) levels under two times the upper limit of normal (2×ULN). METHODS: After liver biopsy and serum virological and biochemical marker screening, patients diagnosed with chronic HBV infection with serum ALT levels under 2×ULN and histological liver inflammation of less than grade G2 were prospectively recruited into this study. Recruitment took place between March 2009 and November 2010 at the Center of Infectious Disease, Sichuan University. Patient virological and biochemical markers, as well as markers of liver inflammation, were monitored. RESULTS: A total of 102 patients were recruited and 68 met the inclusion criteria; the median follow-up was 4.1 years (range 3.9-5.2 years). During follow-up, 41 patients (60.3%) exhibited signs of inflammation. Baseline HBV cccDNA >1 copy/cell (odds ratio 9.43, p=0.049) and liver inflammation grade ≥G1 (odds ratio 5.77, p=0.046) were both independent predictors of liver inflammation. CONCLUSIONS: A higher baseline intrahepatic HBV cccDNA level may increase the risk of liver inflammation. Further investigations will be required to validate HBV cccDNA as an intrahepatic virological marker of patients who require extended outpatient management.

Genotypic resistance profiles in Chinese patients with chronic hepatitis B virus infection and the efficacy of nucleoside analog rescue therapy.

BACKGROUND AND AIMS: The aims of this study were to explore the correlation between chronic hepatitis B virus (HBV) drug-resistant mutation profiles and the efficacy of nucleoside analog rescue therapy in patients with initial antiviral treatment failure. PATIENTS AND METHODS: Patients with initial antiviral therapy failure were recruited between January 2011 and January 2013 from the Division of Infectious Disease, West China Hospital, Sichuan University, Chengdu, People's Republic of China. Following drug-resistant mutation testing, eligible patients received nucleoside analog rescue therapy for 24 weeks. The primary endpoint was rescue therapy efficacy, and the secondary endpoint was adverse events. RESULTS: We recruited 168 patients with chronic HBV infection who had initial antiviral treatment failure. Eighty-nine patients (52.98%) experienced virological breakthrough (group A); 79 patients (47.02%) had partial/null response (group B). Among the patients, 102 (102/168, 60.7%) carried at least one HBV drug resistance mutation. The prevalence of genotypic resistance was significantly higher in group A than in group B (P<0.001). In addition, 118 patients (118/168, 70.2%) achieved undetectable serum HBV DNA with the nucleoside analog rescue therapy. Rescue therapy (P=0.002) and no evidence of genotypic resistance (P=0.001) were related to a higher rate of virological response. CONCLUSION: These data indicate that patients with chronic HBV infection who have initial antiviral therapy failure with or without signs of genotypic resistance may still stand a chance of gaining therapeutic benefit with nucleoside analog rescue therapy.

Serum hepatitis B surface antigen titer and transient elastography in screening for insignificant fibrosis in HBeAg-positive chronic hepatitis B patients.

OBJECTIVE: To explore the predictive value of serum hepatitis B surface antigen (HBsAg) titer and transient elastography in screening for insignificant fibrosis in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients. METHODS: We conducted a cross-sectional study of eligible patients treated from March 2012 to May 2013 at the West China Hospital of Sichuan University. Eligible patients underwent liver transient elastography and liver biopsy. We assessed the serum HBsAg level, serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, HBV genotypes, liver stiffness measurement (LSM) values by transient elastography, and histological fibrosis staging by METAVIR classification. RESULTS: A total of 129 consecutive patients were recruited. The LSM value (P<0.001, odds ratio 14.67, 95% CI 0.158-0.551) and log10HBsAg (P=0.045, odds ratio 4.03, 95% CI 0.136-0.976) correlated with a liver fibrosis score

Impact of mild to moderate elevations of alanine aminotransferase on liver stiffness measurement in chronic hepatitis B patients during antiviral therapy.

AIM: The accuracy of liver stiffness measurement (LSM) in the diagnosis of liver fibrosis is affected by elevated serum alanine aminotransferase (ALT) levels. The aim of this study was to assess the impact of mild to moderate elevations of ALT on LSM in patients with chronic hepatitis B (CHB) during antiviral therapy. METHODS: A total of 58 CHB patients with their ALT levels falling into the range of ×2 to ×10 the upper limit of normal (ULN) were recruited. ALT and LSM values were periodically assessed at baseline and 12, 24 and 48 weeks. RESULTS: The median ALT levels were 153.5 (76-544), 50.5 (11-475), 36.5 (9-265) and 30 (12-239) IU/L at baseline and 12, 24 and 48 weeks, respectively. The corresponding median value of LSM was 8.8 (3.2-47.3), 6.15 (3.2-31.2), 5.9 (3.1-29.1) and 5.5 (2.8-21.5) kpa. However, after the ALT levels were normalized by the treatment, the values of LSM did not vary significantly (6.1 [3.0-17.7] vs 5.25 [2.8-21.5] kpa, P = 0.381). Pretreatment fibrosis stages of liver biopsies corresponded with LSM after ALT normalization rather than baseline LSM (F0-1, 12/27 vs 23/25, P < 0.001). CONCLUSION: The LSM values decreased in parallel with the decline in ALT levels in CHB patients with mild to moderate elevation of ALT. LSM became more accurate when applied to document the liver fibrosis or cirrhosis in CHB patients after the elevated ALT level has been treated to normal level.

Lamivudine plus adefovir or telbivudine plus adefovir for chronic hepatitis B patients with suboptimal response to adefovir.

BACKGROUND: There is no standard management of chronic hepatitis B (CHB) patients with suboptimal response to nucleoside/nucleotide analogues (NAs). This study aimed to evaluate two different NA combination therapies in patients with suboptimal response to adefovir (ADV). METHODS: In this study, 72 CHB patients with suboptimal response to ADV were assessed, with 37 patients receiving lamivudine plus ADV (group A) and 35 patients receiving telbivudine plus ADV (group B). RESULTS: Baseline characteristics between two groups were similar. At month 12, rates of biochemical response (BR) and virological response (VR) were similar between groups A and B (17/19 versus 18/20 for BR, [P=0.269] and 30/37 versus 31/35 for VR [P=0.377]), and cumulative rates of serological response were greater in group B than in group A (10/26 versus 2/28 in hepatitis B e antigen [HBeAg] loss [P=0.006] and 7/26 versus 1/28 in HBeAg/hepatitis B e antibody seroconversion [P=0.022]). After 12-month treatment, 8.1% (3/37) of patients in group A and 5.7% (2/35) of patients in group B had VR; among patients in group A, two had rtM204V/I and rtL180M and one had rtN236T, whereas the two patients in group B had rtM204I+rtL180M. CONCLUSIONS: Both combination therapies led to a significant decrease in HBV DNA. HBeAg serological outcomes were higher with telbivudine plus ADV combination therapy.