The Value of Sacubitril/Valsartan in Acute Anterior Wall ST-Segment Elevation Myocardial Infarction before Emergency Percutaneous Coronary Intervention.

BACKGROUND: Many patients present with heart failure with reduced ejection fraction (HFrEF) after acute anterior wall ST-segment elevation myocardial infarction (STEMI). The purpose of this study was to evaluate the effect of preprocedural sacubitril/valsartan on N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and left ventricular ejection fraction (LVEF) in patients with acute anterior STEMI undergoing percutaneous coronary intervention (PCI). METHODS: We enrolled patients with acute anterior wall STEMI who underwent emergency PCI at The Affiliated Hospital of Putian University from January 2019 to January 2021. Prior to PCI, patients were randomized to receive sacubitril/valsartan or valsartan. Nonculprit lesion vessels that require PCI were excluded. The primary endpoints included changes in NT-pro-BNP, LVEF, and rehospitalization for heart failure (HF) during the follow-up period. RESULTS: Out of 109 patients who were randomized, 55 were assigned to receive sacubitril/valsartan and 54 were assigned to receive valsartan. The decrease in NT-pro-BNP concentrations and the increase in LVEF were significantly greater in the sacubitril/valsartan group than in the valsartan group. CONCLUSIONS: In patients with acute anterior wall STEMI undergoing emergency PCI, preprocedural initiation of sacubitril/valsartan therapy increased LVEF and lower NT-pro-BNP concentrations compared with valsartan therapy.

Predictive Value of Red Blood Cell Distribution Width and Atrial Diameter in Paroxysmal Atrial Fibrillation: A Cross-Sectional Study.

BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia and is associated with deleterious consequences. In addition to worsening a patient's quality of life, AF is associated with stroke, heart failure, and increased mortality. Red blood cell distribution width (RDW) has been associated with an increased risk of death and adverse cardiovascular outcomes, while left atrial enlargement has been linked to atrial fibrillation (AF). However, the relationship among RDW, atrial diameter (AD), and paroxysmal AF is uncertain. The aim of this study was to investigate the relationship among RDW, atrial diameter, and paroxysmal AF. MATERIAL AND METHODS A total of 22 patients with paroxysmal AF and 100 patients with non-AF were included in the study. The demographic variables and baseline clinical characteristics of both groups were analyzed. RESULTS The demographics and comorbidities were comparable between the paroxysmal AF and control groups, except for BMI (body mass index). RDW, high-sensitivity C-reactive protein (hs-CRP) levels, NT-pro-BNP levels, MPV/PLT (mean platelet volume/total platelet count), LAD, RAD, and CHA2DS2-VASc score were higher in the paroxysmal AF group versus the control group (P<0.05). Binary logistic regression analyses demonstrated that RDW (OR: 2.557, 95% CI: 1.481~4.414), Hs-CRP(OR: 1.445, 95% CI: 1.144~1.825), MPV/PLT (OR: 1.342, 95% CI: 1.047~1.720), LAD (OR: 1.068, 95% CI: 1.007~1.132), and CHA2DS2-VASc score (OR: 1.645, 95% CI: 1.042~2.597) were independent predictors for paroxysmal AF (P<0.05, respectively). The ROC analysis showed that the area under the curve for LAD was 0.692, the area under the curve for RAD was 0.566, the area under the curve for RDW was 0.811, and the area under the curve for MPV/PLT was 0.671. CONCLUSIONS LAD, RDW, and MPV/PLT were associated with paroxysmal AF.

Entecavir Combined With Adefovir Ameliorates Patients With Chronic Hepatitis B Who Fail to Respond to Nucleotide (Acid) Analog Monotherapy.

The aim of this study was to evaluate the efficacy and safety of entecavir (ETV) combined treatment with adefovir (ADV) on chronic hepatitic B (CHB) patients who failed to respond to nucleotide (acid) analog (NA) treatment. On this basis, the possible factors in the combined treatment of these patients will be analyzed. The safety, biochemical index, and the possible factors that might affect the ETV and ADV combined treatment at different points in time were retrospectively analyzed. The biochemical index included the following: virological response, hepatitis B virus (HBV) DNA decline, primary nonresponse, biochemical response, and the hepatitis B virus E antigen/hepatitis B virus E antibody seroconversion rate. There were 94 CHB patients and compensated liver cirrhosis patients who received ETV plus ADV treatment for over 12 weeks after failure of treatment with NAs. The authors have also investigated 76 CHB patients (80.9%) and 18 hepatitis B cirrhosis patients (19.1%) in this study. The HBV DNA baseline was 4.4 ± 1.4 log10 IU/mL, and the positive rate of HBeAg before salvage treatment was 78.7% (74/94). The sample sizes were 94, 78, 42, 10, 6, and 1 for follow-up of 24, 48, 96, 144, 192, and 240 weeks, respectively. The virological responses (HBV DNA < 2 log10 IU/mL) and biochemical responses were 52.1%, 74.3%, and 90.4% and 63.1%, 61.6%, and 81.1%, respectively, at 24, 48, and 96 weeks, which showed significant differences (P < 0.001 and P < 0.005, respectively). The HBV DNA decline was presented as mean ± SEM, which were 1.53 ± 1.23, 1.75 ± 1.37, 2.07 ± 1.54, and 2.39 ± 1.77 log10 IU/mL at 12, 24, 48, and 96 weeks, respectively. They showed significant differences compared with the baseline (χ = 8.084, P < 0.05). The rate of primary nonresponse was 30.9% (29/94), and the primary treatment failure rates were 26.6% (25/94), 24.4% (19/78), and 4.8% (2/42) at 24, 48, and 96 weeks, respectively. They all have statistical difference (P = 0.011 < 0.05). There were 23 patients who experienced virological breakthrough after the HBV DNA levels were undetectable, whereas after follow-up for 12-24 weeks, the HBV DNA levels were back to undetectable again. ETV plus ADV treatment is an efficient and safe treatment for CHB and compensated liver cirrhosis patients who experienced NA treatment failure. The high quantity of baseline HBV DNA level is a risk factor for poor efficacy of salvage treatment.

A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study.

BACKGROUND: The ability of circulating microRNAs (miRNAs) to detect preclinical hepatocellular carcinoma has not yet been reported. We aimed to identify and assess a serum miRNA combination that could detect the presence of clinical and preclinical hepatocellular carcinoma in at-risk patients. METHODS: We did a three-stage study that included healthy controls, inactive HBsAg carriers, individuals with chronic hepatitis B, individuals with hepatitis B-induced liver cirrhosis, and patients with diagnosed hepatocellular carcinoma from four hospitals in China. We used array analysis and quantitative PCR to identify 19 candidate serum miRNAs that were increased in six patients with hepatocellular carcinoma compared with eight control patients with chronic hepatitis B. Using a training cohort of patients with hepatocellular carcinoma and controls, we built a serum miRNA classifier to detect hepatocellular carcinoma. We then validated the classifiers' ability in two independent cohorts of patients and controls. We also established the classifiers' ability to predict preclinical hepatocellular carcinoma in a nested case-control study with sera prospectively collected from patients with hepatocellular carcinoma before clinical diagnosis and from matched individuals with hepatitis B who did not develop cancer from the same surveillance programme. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared the miRNA classifier with α-fetoprotein at a cutoff of 20 ng/mL (AFP20). FINDINGS: Between Aug 1, 2009, and Aug 31, 2013, we recruited 257 participants to the training cohort, and 352 and 139 participants to the two independent validation cohorts. In the third validation cohort, 27 patients with hepatocellular carcinoma and 135 matched controls were included in the nested case-control study, which ran from Aug 1, 2009, to Aug 31, 2014. We identified a miRNA classifier (Cmi) containing seven differentially expressed miRNAs (miR-29a, miR-29c, miR-133a, miR-143, miR-145, miR-192, and miR-505) that could detect hepatocellular carcinoma. Cmi showed higher accuracy than AFP20 to distinguish individuals with hepatocellular carcinoma from controls in the validation cohorts, but not in the training cohort (AUC 0·826 [95% CI 0·771-0·880] vs 0·814 [0·756-0·872], p=0·72 in the training cohort; 0·817 [0·769-0·865] vs 0·709 [0·653-0·765], p=0·00076 in validation cohort 1; and 0·884 [0·818-0·951] vs 0·796 [0·706-0·886], p=0·042 for validation cohort 2). In all four cohorts, Cmi had higher sensitivity (range 70·4-85·7%) than did AFP20 (40·7-69·4%) to detect hepatocellular carcinoma at the time of diagnosis, whereas its specificity (80·0-91·1%) was similar to that of AFP20 (84·9-100%). In the nested case-control study, sensitivity of Cmi to detect hepatocellular carcinoma was 29·6% (eight of 27 cases) 12 months before clinical diagnosis, 48·1% (n=13) 9 months before clinical diagnosis, 48·1% (n=13) 6 months before clinical diagnosis, and 55·6% (n=15) 3 months before clinical diagnosis, whereas sensitivity of AFP20 was only 7·4% (n=2), 11·1% (n=3), 18·5% (n=5), and 22·2% (n=6) at the corresponding timepoints (p=0·036, p=0·0030, p=0·021, p=0·012, respectively). Cmi had a larger AUC than did AFP20 to identify small-size (AUC 0·833 [0·782-0·883] vs 0·727 [0·664-0·792], p=0·0018) and early-stage (AUC 0·824 [0·781-0·868] vs 0·754 [0·702-0·806], p=0·015) hepatocellular carcinoma and could also detect α-fetoprotein-negative (AUC 0·825 [0·779-0·871]) hepatocellular carcinoma. INTERPRETATION: Cmi is a potential biomarker for hepatocellular carcinoma, and can identify small-size, early-stage, and α-fetoprotein-negative hepatocellular carcinoma in patients at risk. The miRNA classifier could be valuable to detect preclinical hepatocellular carcinoma, providing patients with a chance of curative resection and longer survival. FUNDING: National Key Basic Research Program, National Science and Technology Major Project, National Natural Science Foundation of China.

[Efficacy of 48-week tenofovir disoproxil fumarate therapy in patients who were unresponsive to nucleoside-analogue treatments].

OBJECTIVE: To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs). METHODS: A total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method. RESULTS: Over the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period. CONCLUSION: For CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.

Efficacy of entecavir treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life.

OBJECTIVE: To analyze the efficacy and safety of entecavir (ETV) treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life. METHODS: We retrospectively analyzed 230 nucleos(t)ide naïve chronic hepatitis B patients who received ETV 0.5 mg/day monotherapy for at least 3 months, of whom 113 were HBeAg positive and 117 were HBeAg negative. The primary endpoints was cumulative probability of achieving a virological response (undetectable serum HBV DNA, <100IU/mL). Secondary endpoints were rates of ALT normalization (ALT < upper limit of normal), HBeAg seroconversion, resistance, and safety. RESULTS: The median follow-up duration was 27.5 months (3-73 months) and mean age was 42 years. With 230, 214, 180, 142, 88, 42 and 11 patients followed-up for at least 3 months,6 months, 1, 2, 3, 4 and 5 years, respectively. In all, Incremental increases were observed in the rates of undetectable HBV DNA. 67.0%, 85.0%, 89.4%, 94.4%, 95.5%, 97.6%, 100% had undetectable HBV DNA at month 3, month 6, 1 year, 2 years, 3 years, 4 years and 5 years. Proportions of patients achieving normal ALT were 73.9%, 85.5%, 82.8%, 89.4%, 80.7%, 85.7%, 100%, respectively. The rate of HBeAg seroconversion reached 21.4% and 15.4% at year2, 3, respectively. One patient achieved HBsAg seroclearance after 1 year, and achieved anti-HBs seroconversion at year 3. Of 180 patients, HBV DNA was detectable (partial virological response, PVR) in 19 patients at year 1 of follow-up, twelve of 14 (85.7%) patients with PVR need more than 1 year of continuous ETV therapy to achieved VR. At baseline, no ETV-resistance was detected in 25 ETV-naïve patients. One patient developed ETV-resistance mutations due to noncompliance. No serious adverse event was reported. CONCLUSION: Long-term ETV treatment of nucleos(t)ide-naïve was effective and safe in real life. Adjustment of ETV monotherapy in nucleos(t)ide-naïve patients with a partial virological response at 1 year may be unnecessary.

Predictive value of serum iron on heart failure in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: In clinical practice, heart failure often occurs after acute myocardial infarction, and a new biomarker for its early prediction is urgently needed. The aim of this study was to investigate the relationship between serum iron and heart failure after acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 41 patients with heart failure after STEMI and 31 controls were included in the study. The demographic variables and baseline clinical characteristics of both groups were analyzed. RESULTS: There were no significant differences between patients with heart failure and controls in terms of demographic characteristics. There were significant differences in terms of serum iron, N terminal pro-B-type natriuretic peptide levels, left atrial diameter, and left ventricular ejection fraction. Binary logistic regression analyses demonstrated that serum iron (odds ratio [OR]: 0.804, 95% confidence interval [CI]: 0.699-0.924) and Tn-I (OR: 1.072, 95% CI: 1.011-1.137) were independent predictors for heart failure (p < .05, respectively). Receiver operating characteristic analysis showed that the area under the curve for serum iron was 0.808 (95% CI: 0.707-0.908, p < .01). The best cutoff value of serum iron was 11.87 µmol/L (sensitivity: 87.1%; specificity: 68.3%). CONCLUSIONS: Patients with heart failure after STEMI have lower serum iron levels than patients without heart failure after STEMI. Serum iron levels are a risk factor for heart failure after STEMI.

Effect of estimated plasma volume status and left atrial diameter on prognosis of patients with acute heart failure.

Objective: Acute heart failure (AHF) is a frequent cardiovascular emergency presenting with high mortality as well as readmission rates. The aim was to investigate the predictive value of estimated plasma volume status (ePVs) and left atrial diameter (LAD) for the prognosis of patients with AHF. Methods: Clinical profiles were collected from 259 cases of AHF patients at the Affiliated Hospital of Putian University between September 2019 and October 2021. Results: Six patients lost follow-up, resulting in 253 patients enrolled. Cardiogenic death and heart failure readmission during follow-up were defined as major cardiovascular events (MACE) group, other patients were defined as Non-MACE group. Apart from age, no significant differences were found between the two groups in demographics and comorbidities. The comparison between the two groups was statistically significant in terms of ePVs, LAD, and N-terminal-pro B-type natriuretic peptide (Nt-pro-BNP). On binary logistic regression analysis, ePVs (OR = 2.061, 95% CI 1.322∼3.214, P = 0.001), LAD (OR = 1.054, 95% CI 1.012∼1.098, P = 0.011), and Nt-pro-bnp (OR = 1.006, 95% CI 1.003∼1.010, P = 0.036) as predicting factors for MACE. Kaplan-Meier analysis indicated that the risk for cardiogenic death increasing with ePVs (p < 0.05). Conclusion: Estimated plasma volume status and LADs have some predictive value in assessing cardiogenic death and heart failure readmission in patients with AHF.

Double Plasma Molecular Adsorption System with Sequential Low-dose Plasma Exchange in Patients with Hepatitis B Virus-related Acute-on-chronic Liver Failure: A Prospective Study.

Background and Aims: To investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-dose plasma exchange (LPE) in treating early hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical data of patients with HBV-ACLF were prospectively collected, including patients in a DPMAS with sequential LPE (DPMAS+LPE) group and those in a standard medical treatment (SMT) group. The primary endpoint was death or liver transplantation (LT) at 12 weeks of follow-up. Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups. Results: After 2 weeks, total bilirubin, alanine aminotransferase, blood urea nitrogen levels, and Chinese Group on the Study of Severe Hepatitis B score, were significantly lower in the DPMAS+LPE group than those in the SMT group (p<0.05). After 4 weeks, laboratory parameters of the two groups were similar. The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks (97.9% vs. 85.4%, p=0.027), but not at 12 weeks (85.4% vs. 83.3%, p=0.687). Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group (p<0.05). Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes, regulation of immune effect response, regulation of endotoxin response, and glial cell proliferation. Conclusion: DPMAS+LPE significantly improved the 4-week cumulative survival rate, and ameliorated the inflammatory response in patients. DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.

The Significance of Apolipoprotein-A in the Long-Term Death of Patients with STEMI.

OBJECTIVE: To analyze apolipoprotein-A for its predictive value for long-term death in individuals suffering from acute ST-segment elevation myocardial infarction following percutaneous coronary intervention. METHODS: We selected patients suffering from acute ST-segment elevation myocardial infarction who underwent emergency PCI at the Affiliated Hospital of Putian University from January 2017 to August 2019. The patients were divided into a high-Apo-A group and low-Apo-A group, and we observed all-cause deaths of patients in the 2 groups within 2 years. RESULTS: The ROC curve analysis indicated the best critical value for predicting 2-year mortality as 0.8150 (area under the curve was 0.626, sensitivity 75.1%, and specificity 51.9%). There was no statistical difference among the two groups in gender, age, lesion vessel, and comorbidities. The two groups had statistically significant differences in apolipoprotein-B/A, high-density lipoprotein, apolipoprotein-A, and hypersensitivity C-reactive protein. Correlation analysis showed a significant negative correlation between apolipoprotein-A and hypersensitive C-reactive protein. The results of the 24-month analysis indicated the incidence of all-cause mortality as higher in the low-Apo-A group, and Kaplan-Meier survival analysis showed the same trend. CONCLUSION: Apolipoprotein-A can predict the potential for long-term mortality among individuals having acute ST-segment elevation myocardial infarction.

Predictive value of neutrophil to lymphocyte ratio and red cell distribution width on death for ST segment elevation myocardial infarction.

There are many clinical scoring criteria for predicting the risk of death in patients with acute ST-segment elevation myocardial infarction (STEMI), but most of the indicators are complex to calculate and are not suitable for use in primary hospitals. Neutrophil to lymphocyte ratio (NLR) and red cell distribution width (RDW) are blood routine indicators that are easy to obtain and may help primary hospitals to evaluate the risk of death in patients with STEMI. Our aim was to explore the predictive value of NLR combined with RDW in the long-term prognosis of patients with STEMI after emergency percutaneous coronary intervention (PCI). A total of 181 patients with STEMI who underwent emergency PCI in the Affiliated Hospital of Pu-tian University from January 2017 to August 2018 were selected. Clinical profile, prognosis of all patients were collected. P value < 0.05 was considered significant. In all patients, cardiovascular death during the follow-up period was defined as cardiovascular death group, and surviving during the follow-up period was defined as survival group. There were no significant differences in demography and comorbidities between the two groups. The differences between the two groups in NLR, RDW, C-reactive protein, N-terminal-pro B type natriuretic peptide were statistically significant (P < 0.01). Binary logistic regression analysis showed that NLR (OR = 1.122, 95% CI 1.041 ~ 1.210, P = 0.003) and RDW (OR = 1.288, 95% CI 1.126 ~ 1.472, P = 0.0005) were important predictors of mortality in patients with STEMI (P < 0.05). Kaplan-Meier analysis showed that as the NLR increased, the risk of death increased (P < 0.001). In conclusion, NLR and RDW are independent predictors of cardiovascular death in patients with STEMI, and they have a certain predictive value.

Inappropriate cessation of nucleos(t)ide analog associated with reduced liver transplant-free survival in patients with HBV-related acute on chronic liver failure.

The inappropriate cessation of nucleos(t)ide analog (NA) therapy may lead to acute exacerbations of chronic hepatitis B virus (HBV) infection, acute-on-chronic liver failure (ACLF), and even death. This study aims to elucidate the association between inappropriate NA cessation and prognosis in patients with HBV-ACLF. A total of 901 patients with ACLF were enrolled and stratified into inappropriate NA cessation and non-NA cessation group. Clinical characteristics and prognosis between the two groups were compared. The association between inappropriate NA cessation and the prognosis of patients with HBV-ACLF was evaluated using Cox proportional hazard models after propensity score matching (PSM). NA cessation was identified in 132 patients (NA cessation group), while 769 patients were triggered by other factors (non-NA cessation group). The 28- and 90-day liver transplant-free survival rates were higher in patients with non-NA cessation than in those with NAs cessation (78.3 % vs. 62.1 %, P < 0.001; 62.8 % vs. 44.7 %, P < 0.001). The need for liver transplantation was significantly higher in the NA cessation group compared with the non-NAs cessation group (21.2 % vs. 7.0 %, P < 0.001). The Kaplan-Meier curve showed that inappropriate NA therapy discontinuation had reduced 28- and 90-day live transplant-free survival compared with other precipitating events prior to PSM (all P < 0.001). After matching, the 28- and 90-day transplantation-free survival was also significantly lower in the NA cessation group vs. the non-NA cessation group (P = 0.012 and P = 0.022). In conclusion, the inappropriate cessation of NA therapy is associated with reduced liver transplant-free survival in patients with HBV-related ACLF.

Prediction Model of HBsAg Seroclearance in Patients with Chronic HBV Infection.

BACKGROUND: Prediction of HBsAg seroclearance, defined as the loss of circulating HBsAg with or without development of antibodies for HBsAg in patients with chronic hepatitis B (CHB), is highly difficult and challenging due to its low incidence. This study is aimed at developing and validating a nomogram for prediction of HBsAg loss in CHB patients. METHODS: We analyzed a total of 1398 patients with CHB. Two-thirds of the patients were randomly assigned to the training set (n = 918), and one-third were assigned to the validation set (n = 480). Univariate and multivariate analysis by Cox regression analysis was performed using the training set, and the nomogram was constructed. Discrimination and calibration were performed using the training set and validation set. RESULTS: On multivariate analysis of the training set, independent factors for HBsAg loss including BMI, HBeAg status, HBsAg titer (quantitative HBsAg), and baseline hepatitis B virus (HBV) DNA level were incorporated into the nomogram. The HBsAg seroclearance calibration curve showed an optimal agreement between predictions by the nomogram and actual observation. The concordance index (C-index) of nomogram was 0.913, with confirmation in the validation set where the C-index was 0.886. CONCLUSIONS: We established and validated a novel nomogram that can individually predict HBsAg seroclearance and non-seroclearance for CHB patients, which is clinically unprecedented. This practical prognostic model may help clinicians in decision-making and design of clinical studies.

Barriers to hepatitis C virus treatment in Guangdong Province.

BACKGROUND: The objective of this study is to analyze the causes of nontreatment among patients with hepatitis C virus (HCV) infection and increase the cure rate of chronic hepatitis C in Guangdong Province. METHODS: We performed both retrospective survey and prospective study in a cohort of 435 outpatients in our center to analyze the subjective and objective causes of HCV non-treatment. RESULTS: Among 1,931 patients, 435 did not receive anti-viral therapy (AVT), and, in 37 of these patients, the virus load was persistently negative. In the remaining 398 patients, HCV RNA repeatedly tested positive. The causes of nontreatment in these patients included economic constraints (n=77, 17.7%); old age, fear of treatment-related side effects, uncertainty (n=46, 10.6%); fear of potential adverse effects on fertility (n=37, 8.5%); fear of interferon side-effects (n=21, 4.8%); and dosing inconvenience during study or work (n=9, 2.1%). In addition, 137 patients (31.5%) had medical contraindications including decompensated hepatic cirrhosis (n=55, 12.6%), uncontrolled autoimmune diseases (e.g., autoimmune hepatitis and systemic lupus erythematosus) (n=19, 4.4%), renal dysfunction (n=21, 4.8%), thyroid disease (hyperthyroidism) (n=16, 3.7%), depression (n=14, 3.2%), uncontrolled diabetes (n=5, 1.1%), severe lung disease (e.g., active tuberculosis) (n=4, 0.9%), symptomatic heart disease (n=3, 0.7%), alcoholism (n=15, 3.4%), drug addiction (n=31, 7.1%), lack of physician recommendation (n=2, 0.5%), and unknown reasons (n=23, 5.3%). CONCLUSIONS: The low rate of AVT in HCV-infected patients is related to many factors. In Guangdong province, HCV patients do not receive AVT mainly due to economic constraints, patients' fear of side effects, and the presence of contraindications.

Efficacy of tenofovir disoproxil fumarate switch therapy in chronic hepatitis B patients with suboptimal response to adefovir-based combination therapy.

In the present study, the efficacy and safety of tenofovir disoproxil fumarate (TDF) switch therapy were assessed in patients with chronic hepatitis B exhibiting a suboptimal response to adefovir (ADV)-based combination therapy. First, the efficacy of the TDF switch therapy was retrospectively evaluated in 50 patients with chronic hepatitis B who failed to respond to ADV-based combination treatment. Among those, 48 patients with a median age of 35 years were hepatitis B e antigen (HBeAg)-positive and 17, 14 and 19 patients were previously treated with lamivudine (LAM) plus ADV, telbivudine plus ADV and entecavir (ETV) plus ADV, respectively. A total of 41 patients were treated with TDF alone and 9 with TDF plus ETV. The median time of follow-up was 102 weeks. The primary end-point was the cumulative probability of achieving a complete virologic response (CVR). The secondary end-points were the rate of alanine aminotransferase (ALT) normalization, HBeAg seroconversion in HBeAg-positive patients, and the plasma levels of creatinine and creatine kinase. The mean serum hepatitis B virus DNA levels prior to initiation of the TDF switch therapy were 4.8±1.6 log10IU/ml. The cumulative probability of achieving a VR at 24, 48, 96 and 108 weeks was 52.0, 76.0, 89.8 and 94.9%, respectively. The cumulative probability of normalization of ALT at 12, 24, 36, 48, 60,72, 84, 96, 108, 120 and 132 weeks was 34, 44, 50, 58, 66, 70, 74, 80, 90, 92 and 94%, respectively. HBeAg seroconversion was achieved in 5 patients. During the follow-up, 6 patients suffered from a virologic breakthrough, 3 patients failed to respond to the TDF treatment and the remaining patients were able to obtain VR following the continuation of TDF treatment. Slightly elevated serum levels of creatinine were observed in one patient, whereas creatine kinase activity did not increase in any of the subjects. In conclusion, TDF switch therapy is efficient and safe for patients with chronic hepatitis B with a suboptimal response to ADV-based combination therapy.

Circulating FGF19 closely correlates with bile acid synthesis and cholestasis in patients with primary biliary cirrhosis.

BACKGROUND AND AIM: Bile acid (BA) synthesis in the liver is regulated by Fibroblast Growth Factor 19 (FGF19) secreted from the ileum as an enterohepatic feedback mechanism. Although FGF19 mRNA is absent in normal liver, FGF19 gene expression was reported to increase in response to both extrahepatic and intrahepatic cholestasis. The impact of upregulated FGF19 expression on BA synthesis is unclear and the overall role of circulating FGF19 and BA synthesis under cholestatic conditions needs to be further investigated. METHODS: BA synthesis was directly quantified by measuring serum concentrations of 7alpha-hydroxycholest-4-en-3-one (C4), along with serum FGF19 and other parameters, in 44 patients with primary biliary cirrhosis (PBC) and 10 healthy subjects. RESULTS: Serum C4 were substantially lower, while those of FGF19 were higher, in cirrhotic PBC patients, as compared to those of either healthy or non-cirrhotic PBC patients. Analyses of the relationships between circulating FGF19, BA synthesis and cholestasis revealed that circulating FGF19 was strongly correlated with BA synthesis (r = -0.735, p<0.0001) and the severity of cholestasis (r = 0.590, p<0.001). Moreover, BA synthesis was found to be strongly correlated with the degree of cholestasis (r = 0.522, p = 0.0005). CONCLUSION: These findings demonstrate that the regulation of BA synthesis in response to cholestasis is primarily controlled by circulating FGF19 and that under cholestatic conditions, the FGF19-BA synthesis feedback mechanism remains intact. Administering FGF19, or suitable mimetic, as a pharmacological intervention to increase circulating levels of FGF19 and suppress BA synthesis by inhibiting CYP7A1 gene expression is likely to provide therapeutic benefits for many PBC patients.

TDF Monotherapy Is Effective Regardless of Prior Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patients in China.

BACKGROUND/AIMS: Many patients had to transfer to tenofovir disoproxil fumarate (TDF) if there is other nucleos(t)ide analogue (NA) resistance. We aimed to investigate antiviral effects of TDF monotherapy between NA-naive and NA-experienced chronic hepatitis B (CHB) patients in China. METHODS: A total of 102 NA-naive and NA-experienced CHB patients with TDF monotherapy (300 mg/day) were retrospectively analyzed for useful parameters up to 72 weeks. RESULTS: There were 36 and 66 patients with matched HBV DNA baseline level in NA-naïve and NA-experienced group, respectively. There were no significant differences between NA-naïve and NA-experienced groups in HBV DNA levels (all P > 0.05) and HBV DNA undetectable rates (all P > 0.05) at all time points. At the end of follow-up, HBV DNA undetectable rates in NA-naïve and NA-experienced group were 96.2% (25/26) and 91.8% (45/49), respectively (P = 0.476). Baseline HBV DNA level was the only independent predictor for HBV DNA negative time (P = 0.018). In addition, 27.8% (5/18) and 11.4% (4/35) achieved HBeAg seroconversion at the end of the follow-up, respectively (P = 0.133). CONCLUSIONS: TDF monotherapy was effective regardless of prior NA experienced. Baseline HBV DNA was a key predictive factor for HBV DNA negative time in TDF monotherapy.

Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients.

BACKGROUND AND OBJECTIVE: The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. METHODS: Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. RESULTS: In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4). CONCLUSIONS: RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

Hepatitis C virus load in parenchyma cells correlates with hepatic injury in infected patients.

The association between serum hepatitis C virus (HCV) load and hepatic injury in HCV-infected patients has been extensively investigated. The present study aimed to investigate the association between HCV load in hepatic parenchyma cells and hepatic injury in HCV-infected patients. A total of 56 HCV-infected patients were included in the present retrospective study. The serum HCV mRNA was determined using quantitative polymerase chain reaction, while the hepatic parenchyma cell volume and HCV mRNA in hepatic parenchyma cells were also determined. Hepatic injury was evaluated on the basis of the severity of inflammation and fibrosis. The results demonstrated that there were evident differences in the mean serum HCV RNA levels and the HCV load/parenchyma cell volume among the various grades of hepatic inflammation (G1-G4) when groups with the least and most inflammation were compared (G1 vs. G4; P<0.05). Significant differences in the HCV load existed between groups divided according to the fibrosis grade; in addition, differences existed between fibrosis grades S1 and S2, and S2 and S4 when comparing serum HCV RNA levels (P<0.05). Similarly, differences existed between every two fibrosis stages (S0 vs. S4, S2 vs. S3, and S2 vs. S4; P<0.05) when viral loads and parenchyma cell volumes were compared (F=2.860, P<0.05). Furthermore, the fibrosis staging was correlated with the viral load/parenchyma cell volume (F=2.670, P<0.05). In conclusion, hepatic fibrosis grade was found to be associated with HCV load in parenchyma cells. The results of the present study demonstrated that the viral load in parenchyma cells is a more appropriate index compared with the serum viral load for evaluating HCV replication in hepatocytes, and may function as an important factor in HCV-infected hepatic injury evaluation.

[The clinical features and natural history of post-transfusion hepatitis C].

OBJECTIVE: To study the clinical features and natural history of post-transfusion hepatitis C (PTHC). METHODS: Ninety-nine post-transfusion hepatitis C patients were analyzed using retrospective and prospective study and follow-up. RESULTS: (1) Ninety-nine post-transfusion HCV patients were infected during 1989-1994, mostly between 1990-1992. (2) Ninety patients were diagnosed as chronic hepatitis C, and 9 as hepatic cirrhosis (period of compensation). (3) The intervals between their transfusions and their initial diagnoses of PTHC were 7.4+/-6.6 years in all 99 patients, and the intervals in 9 cirrhosis patients were 12.7+/-5.8 years. (4) Among 63 male patients, 59 cases were chronic hepatitis C and 4 were cirrhosis while among 36 female patients, 31 were chronic hepatitis C and 5 were cirrhosis. There was no significant difference of the ratio for hepatitis C and cirrhosis between the male and female patients (P>0.05). (5) Repeat abnormal liver function occurred accompanied with a fluctuation of ALT elevation in those patients with cirrhosis. (6) No patient developed hepatic carcinoma during the study period. CONCLUSIONS: (1) The possibility of HCV infection by transfusion has declined greatly since 1995 in Guangzhou. (2) Nine of the 99 (9.1%) chronic HCV-infected patients developed a compensated cirrhosis after 12.7+/-5.8 years. (3) For those PTHC patients with repeat abnormal liver functions, interferon combined with ribavirin is recommended to prevent the development of cirrhosis.