[A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA].

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

[Impact of treatment compliance in chronic hepatitis B].

The incidence rate of chronic hepatitis B remains high in China. Antiviral therapy can significantly reduce the risk of progressive liver disease and hepatocellular carcinoma in patients with chronic hepatitis B. However, all current antiviral treatments can only inhibit HBV replication and not completely eliminate the hepatitis B virus, so antiviral therapy for chronic hepatitis B is probably a long-term or even lifelong treatment. Antiviral therapy compliance is essential for achieving long-term clinical benefits and preventing nucleot(s)ide drugs resistance. Herein, we analyzed the relevant factors of antiviral therapy compliance and their impact on CHB treatment and explored feasible programs that can improve compliance with nucleot(s)ide drug treatment by conducting a literature search using PubMed and Scopus with search terms including hepatitis B, compliance, nucleot(s)ide drugs, antiviral therapy, viral suppression, and drug resistance.

[Current concerns and considerations regarding mesenchymal stem cells therapy in perplexing severe liver diseases].

Stem cells are type of cells that have unlimited self-renewal and multi-differentiation potential under specific conditions. Stem cell-based therapeutic techniques can provide new methods for the treatment of perplexing severe liver diseases. Umbilical cord mesenchymal stem cells are currently considered as ideal stem cells due to their low immunogenicity, convenient materials, abundant sources and advantage of no ethical controversy in the clinical treatment of diseases. Presently, there is a large number of basic and clinical application evidence, which suggests that mesenchymal stem cells can significantly improve the condition and outcome of end-stage liver diseases such as liver cirrhosis and liver failure, and its mechanism of action may include hepatocyte-like cells differentiation, immune function regulation, exosome secretion, etc. This paper briefly summarizes the current theories and clinical research status of mesenchymal stem cells application, as well as the therapeutic clinical trial issues and concerns that needs to be resolved during the perplexing severe liver diseases process.

Efficacy and safety of three adefovir-based combination therapies in HBeAg-positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy.

Although high potent nucleos(t)ide analogues are strongly recommended as first-line therapy for chronic hepatitis B (CHB) in China, some patients are still being treated with adefovir disoproxil (ADV), especially those low-income patients whose health insurance could not reimburse the drug cost. Therefore, the management of patients who have failed ADV therapy or who sustained renal damage during ADV therapy remains an important clinical problem in China. This retrospective study aimed to compare the efficacy and safety of lamivudine (LAM), telbivudine (LdT) or entecavir (ETV) add-on strategies to optimize the treatment of patients with prior suboptimal response to ADV monotherapy. A total of 277 eligible patients were included in this study, and the baseline characteristics were similar among the LAM + ADV (n = 116), LdT + ADV (n = 72) and ETV + ADV (n = 89) groups. At week 96, both the proportion of undetectable HBV DNA (81.03% for LAM + ADV, 84.72% for LdT + ADV and 88.76% for ETV + ADV; P = .317) and ALT elevation (5.17% for LAM + ADV, 4.17% for LdT + ADV and 4.49% for ETV + ADV; P = 1.000) were similar among the three groups; also, a significant decline in liver stiffness was observed in each group from baseline to week 96. At week 96, the rate of HBeAg seroconversion was significantly higher in LdT + ADV than in LAM + ADV (26.39% vs 13.79%, P = .031) and ETV + ADV (26.39% vs 10.11%, P = .007). During the 96 weeks, no obvious renal injury was reported in any of the three groups, but an improvement in eGFR was found in LdT + ADV compared with LAM + ADV and ETV + ADV. In summary, all three combination strategies provide good control of virus replication, but the LdT + ADV combination therapy may yield better HBeAg seroconversion and eGFR improvement.

Intrahepatic IFN-alpha expression in liver specimens from HBV-infected patients with different outcomes.

BACKGROUND: Interferon-alpha (IFN-α), an active cytokine, plays an important role in antiviral host responses, including protection against hepatitis B virus (HBV) infection. This study was designed to investigate the correlation between intrahepatic IFN-α expression levels and disease severity using liver biopsy specimens from HBV-infected patients with different outcomes. PATIENTS AND METHODS: Immunohistochemistry (IHC) was performed to detect intrahepatic IFN-α expression in liver biopsy specimens obtained from 69 HBV-infected patients with different outcomes (including 23 cases with chronic hepatitis B [CHB], 18 cases with severe hepatitis B [SHB], and 28 cases with liver cirrhosis [LC]). In situ hybridization (ISH) was carried out to measure the levels of HBV DNA in liver samples. In addition, the liver specimens of 33 healthy liver transplant donors without detectable liver diseases comprised a normal control (NC) group. RESULTS: The intrahepatic expression levels of IFN-α were higher in the HBV-infected patients than the NC group (p = 0.001). Intrahepatic IFN-α expression was also significantly higher in the SHB and CHB groups compared to the NC group (p = 0.001 and p = 0.001, respectively), while the intrahepatic HBV DNA levels of the SHB patients were higher than those of LC patients (p = 0.013). Furthermore, intrahepatic IFN-α expression was positively correlated with serum alanine aminotransferase (ALT) levels in CHB patients; no significant correlations were discovered between intrahepatic IFN-α expression and intrahepatic HBV DNA levels in all other sub-groups. CONCLUSIONS: Intrahepatic IFN-α expression may correlate with liver inflammation after hepatitis B virus infection, and IFN-α may play a vital role in the occurrence of SHB.

The current status of combination therapy of chronic hepatitis B.

In the past decade, the treatment of chronic Hepatitis B (CHB) has been revolutionized by the increased availability of effective antiviral agents. However, there is an alarming of the increasing rates of viral resistance and suboptimal response in CHB patients with single drug therapy. Recently, the strategy of combination therapy for CHB has been proposed and concerned by clinicians. In this review, using PubMed and web of science as main searching tools, we evaluated various latest research reports on combination therapy for CHB, and made a summary of the progress of combination antiviral therapy and outline areas that need to be addressed in the future.

Seroprevalence of hepatitis B virus markers in individuals for physical examination in West China Hospital, China.

BACKGROUND: Hepatitis B virus (HBV) is the major cause of chronic hepatitis,cirrhosis, and hepatocellular carcinoma. The global epidemiological scenario of HBV infection has been changing rapidly over the last two decades due to an effective immunization programme initiated by the World Health Organization. The objective of this study is to estimate the prevalence of HBV in apparently adult people who were taken health examination in our Hospital. METHODS: A cross-sectional seroprevalence analysis of hepatitis B virus infection was performed in 12037 adult residents (aged > or =18 years) in Chengdu, who visited Health Examination Center of West China Hospital of Sichuan University for routine medical check-up during the period from March to December 2008. A structured medical form was used to collect data on demographic characteristics and risk factors. ELISA was used to test sera for HBV markers. Descriptive and logistic regression models were used for analysis. RESULTS: A total of 12,037 urban residents were involved. Prevalence of positive HBsAg was 6.1%, lower than the level of national seroepidemiological survey in (7.18%). Among HBsAg negative people, anti-HBs and anti-HBc was 60.2% and 13.6% respectively. There was a maximum between 18 to 29 years of age (61.8%) in anti-HBs positive people. Multivariate conditional logistic regressive analysis showed that, except for blood and vertical transmission, factors of male gender (OR, 1.876; 95% CI, 1.519-2.316; P < 0.001) and alcohol intake (OR, 0.689; 95% CI, 0.571-0.832; P < 0.001) were associated with a higher risk of positive HBsAg. CONCLUSIONS: Among the medical examination people in Chengdu, HBsAg positive rate was lower than the national general population, the epidemiological characteristics of hepatitis B has been changed, because of vacination policies to the newborn; therefore, the necessity to continue to carry on the vaccination program.

Combination of Lamivudine and adefovir therapy in HBeAg-positive chronic hepatitis B patients with poor response to adefovir monotherapy.

At present, there is no consensus treatment for patients who have poor response to Adevofir dipivoxil (ADV) monotherapy and no ADV-associated mutation. The purpose of this study was to evaluate the effect of a new therapeutic strategy combining Lamivudine (LAM) and ADV in patients with HBeAg-positive chronic hepatitis B (CHB) and poor response to ADV monotherapy. Thirty-one patients with chronic hepatitis B with HBV DNA > or = 10(4) copies/mL after 48 weeks of ADV monotherapy were included and received ADV plus LAM for 24 weeks. Compared with ADV monotherapy, ADV + LAM had an improved response rate at weeks 12 and 24 - compared with baseline, the median decrease in HBV-DNA level at week 12 and 24 were 1.27 and 2.03 log respectively. The virological response (VR) rate (HBV-DNA level <10(3) copies/mL) was 6.5% and 35.5% at weeks 12 and 24, respectively; the biochemical response (BR) rate (normalization of alanine aminotransferase levels) was 67.8% and 100%, respectively; the HBeAg loss rate was 6.9% and 34.5%, respectively; and the seroconversion rate (from HBeAg to HBeAb) was 3.5% and 6.9% respectively. No ADV-associated mutation was detected at baseline. After combination therapy for 24 weeks, no LAM-resistant or ADV-resistant mutations were detected. Only one patient had a mild adverse reaction. In conclusion, optimization of therapy combining LAM and ADV may be a good choice for patients with hepatitis B who have a poor response to ADV monotherapy.

Myocardial viability studies using fluorine-18-FDG SPECT: a comparison with fluorine-18-FDG PET.

UNLABELLED: Multidetector SPECT systems equipped with a high-energy, or 511-keV collimator, have been proposed to offer a less expensive alternative to PET in myocardial viability studies with [18F]FDG. The objectives of this investigation included: (a) measuring the physical imaging characteristics of SPECT systems equipped with either a high-energy general-purpose collimator (HE), or the dedicated 511-keV collimator (UH), when imaging 511-keV photons, and comparing them with conventional FDG PET; and (b) directly and quantitatively comparing the diagnostic accuracy of SPECT, with either an UH or HE collimator, to that of PET in myocardial viability studies using 18F-FDG. METHODS: Physical imaging characteristics of SPECT and PET were measured and compared. Both SPECT and PET studies were performed in two groups of 18 patients each, with Group I using HE SPECT and Group II using UH SPECT. Myocardial perfusion studies were also performed using 82Rb PET at rest and during dipyridamole stress to identify areas of persistent hypoperfusion. For each myocardial region with a persistent perfusion defect, a perfusion-metabolism match or mismatch pattern was established independently, based on the results of 18F-FDG SPECT as well as PET. RESULTS: PET is superior to SPECT in all physical imaging characteristics, particularly in sensitivity and contrast resolution. PET had a sensitivity 40-80 times higher than that of SPECT, and its contrast resolution was 40-100% better than SPECT. Between FDG-SPECT using an HE collimator and that using a 511-keV collimator, the latter showed marked reduction in septal penetration (from 56% to 38%), improvement in spatial resolution (from 17 mm to 11 mm FWHM) as well as contrast resolution (from 34% to 45%), while suffering reduced system sensitivity (from 75 to 34 cpm/microCi). Patient studies demonstrated that although FDG-SPECT, using a HE or UH collimator, provided concordant viability information as FDG PET in a large majority of myocardial segments with persistent perfusion defects (88% and 90%, respectively), there is an excellent statistical agreement (kappa = 0.736) between SPECT with UH collimator and PET, while the agreement between SPECT using HE collimator and PET are moderate (kappa = 0.413). CONCLUSION: Despite its markedly inferior physical imaging characteristics compared with PET, SPECT with the dedicated 511-keV collimator offers a low-cost, practical alternative to PET in studying myocardial viability using [18F]FDG. SPECT systems with a high-energy, general-purpose collimator, on the other hand, are inadequate in such studies.

Regional body FDG-PET in postoperative recurrent hyperparathyroidism.

PURPOSE: The use of preoperative imaging studies in patients with persistent or recurrent hyperparathyroidism after initial operation is generally accepted to improve the success rate and minimize the morbidity from reoperative surgery. The purpose of this study was to define the performance of FDG-PET for the localization of hyperfunctioning parathyroid tissue prior to reoperation. METHOD: Twenty patients with biochemical evidence of recurrent or persistent hyperparathyroidism following previous neck surgery were investigated. Regional body PET imaging of the neck and upper chest (axial field of view 27.5 cm) was acquired 45 min after 5-10 mCi FDG was given intravenously. RESULTS: Subsequent surgery revealed solitary parathyroid adenomas in 14 patients, seven hyperplastic glands in 2 patients, and parathyroid carcinoma in 1 patients. FDG-PET correctly identified 79% (11/14) of the parathyroid adenomas, 29% (2/7) of the hyperplastic glands, and the parathyroid carcinoma. FDG-PET was negative in 79% (30/38) of the surgically identified normal parathyroid glands. Eight false-positive findings led to a positive predictive value of 64%. CONCLUSION: These preliminary data suggest that regional body FDG-PET is a promising procedure in the evaluation of patients with persistent or recurrent postoperative hyperparathyroidism.

Comparison of FDG-PET and sestamibi-SPECT in primary hyperparathyroidism.

UNLABELLED: Preoperative localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism has been a longstanding diagnostic challenge. This study directly compared FDG-PET and sestamibi-SPECT for preoperative detection of abnormal parathyroid tissue. METHODS: Twenty-one consecutive patients with primary hyperparathyroidism were studied prospectively before surgical neck exploration. SPECT of the neck and chest was performed at 15 min and 2 hr after intravenous 99mTc-sestamibi. Regional body PET was performed 45 min after intravenous FDG. RESULTS: Surgery revealed 19 solitary parathyroid adenomas, 2 parathyroid adenomas in one patient; and 3 hyperplastic parathyroid glands in one patient, and 51 normal parathyroid glands. The diagnostic sensitivities for detection of parathyroid adenomas of 43% (9 of 21) for dual-phase sestamibi-SPECT and 86% (18 of 21) for FDG-PET were significantly different (p < 0.001). The difference in diagnostic specificities of 78% (40 of 51) for FDG-PET and 90% (46 of 51) for dual-phase sestamibi-SPECT approached statistical significance (p = 0.063). CONCLUSION: This study demonstrates that FDG-PET is more sensitive than sestamibi-SPECT in the preoperative localization of parathyroid adenomas in patients with primary hyperparathyroidism.

Is image subtraction necessary in the clinical interpretation of single-day split-dose stress cerebral perfusion single-photon emission tomography using technetium-99m compounds?

The aim of this study was to validate a simplified semiquantitative method of evaluating a single-day stress cerebral perfusion test to obtain cerebrovascular reserve capacity (CVRC) for routine clinical uses. A split-dose protocol was tested in 36 pairs of technetium-99m hexamethylpropylene amino oxime baseline (low dose) and acetazolamide (high dose) stress brain single-photon emission tomographic (SPET) studies from 16 patients with cerebrovascular disease. The images were displayed on a semiquantitative color scale with (corrected) and without (uncorrected) image subtraction, dose adjustment, and decay correction. The representative CVRC was determined by placing 3x3 pixel regions of interest on midthalamic and midcerebellar slices. The corrected and uncorrected relative changes in CVRC were correlated using linear regression. The relative changes of corrected (x) and uncorrected (y) CVRC by quantitative analysis were highly correlated in a linear fashion (y=0.67x+0.002, r=0.998, P<0.0005). As predicted by theory, the slope was related to the ratio of split dose and independent of ROI sampling. Single-day split-dose stress brain SPET can be accurately performed without image subtraction and complicated dose adjustment or decay correction for clinical studies.

Present assessment of myocardial viability by nuclear imaging.

Prospective delineation of viable from nonviable myocardium in patients with coronary artery disease in an important factor in deciding whether a patient should be revascularized or treated medically. Two common techniques--single-photon emission computed tomography (SPECT) and positron-emission computed tomography (PET)--are used in nuclear medicine using various radiopharmaceuticals for the detection of myocardial viability in patients. Thallium-201 (201Tl) and technetium-99m (99mTc)-sestamibi are the common radiopharmaceuticals used in different protocols using SPECT, whereas fluoride-18 (18F)-fluorodeoxyglucose (FDG) and rubidium-82 (82Rb) are most widely used in PET. The SPECT protocols involve stress/redistribution, stress/redistribution/reinjection, and rest/redistribution imaging techniques. Many studies have compared the results of 201Tl and (99mTc)-sestamibi SPECT with those of FDG PET; in some studies, concordant results have been found between delayed thallium and FDG results, indicating that 201Tl, although considered a perfusion agent, shows myocardial viability. Discordant results in a number of studies have been found between sestamibi and FDG, suggesting that the efficacy of sestamibi as a viability marker has yet to be established. Radiolabeled fatty acids such as iodine-123 (123I)-para-iodophenylpentadecanoic acid and carbon-11 (11C)-palmitic acid have been used for the assessment of myocardial viability with limited success. 11C-labeled acetate is a good marker of oxidative metabolism in the heart and has been used to predict the reversibility of wall motion abnormalities. (18F)-FDG is considered the marker of choice for myocardial viability, although variable results are obtained under different physiological conditions. Detection of myocardial viability can be greatly improved by developing new equipment and radiopharmaceuticals of better quality.

Measurement of cardiac output with first-pass determination during rubidium-82 PET myocardial perfusion imaging.

In addition to providing useful clinical information, cardiac output determined during rubidium-82 positron emission tomographic (PET) myocardial perfusion studies can be used in the measurement of absolute regional myocardial blood flow using Sapirstein's method. This investigation was conducted to compare cardiac output values obtained by post-processing data acquired in a list mode PET myocardial perfusion study with those obtained using a technetium-99m-labeled red blood cell method on the same patients. Results from 14 patients showed that cardiac output can be accurately measured simultaneously in a 82Rb PET myocardial study, allowing determination of multiple perfusion and functional parameters of the heart, thus improving the cost-effectiveness of the 82Rb PET study.

Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging.

UNLABELLED: PET is useful in the presurgical evaluation of temporal lobe epilepsy. The purpose of this retrospective study is to assess the clinical use of statistical parametric imaging in predicting surgical outcome. METHODS: Interictal 18FDG-PET scans in 17 patients with surgically-treated temporal lobe epilepsy (Group A-13 seizure-free, group B = 4 not seizure-free at 6 mo) were transformed into statistical parametric imaging, with each pixel representing a z-score value by using the mean and s.d. of count distribution in each individual patient, for both visual and quantitative analysis. RESULTS: Mean z-scores were significantly more negative in anterolateral (AL) and mesial (M) regions on the operated side than the nonoperated side in group A (AL: p < 0.00005, M: p = 0.0097), but not in group B (AL: p = 0.46, M: p = 0.08). Statistical parametric imaging correctly lateralized 16 out of 17 patients. Only the AL region, however, was significant in predicting surgical outcome (F = 29.03, p < 0.00005). Using a cut-off z-score value of -1.5, statistical parametric imaging correctly classified 92% of temporal lobes from group A and 88% of those from Group B. CONCLUSION: The preliminary results indicate that statistical parametric imaging provides both clinically useful information for lateralization in temporal lobe epilepsy and a reliable predictive indicator of clinical outcome following surgical treatment.

The incidence of scintigraphically viable and nonviable tissue by rubidium-82 and fluorine-18-fluorodeoxyglucose positron emission tomographic imaging in patients with prior infarction and left ventricular dysfunction.

BACKGROUND: Although reversible perfusion defects, perfusion-metabolism mismatch and match patterns are important for differentiating viable from nonviable myocardium, the frequency of these scintigraphic patterns has not been reported. The study objective was to establish the incidence of these scintigraphic patterns to estimate the clinical need for metabolic positron emission tomography for evaluating tissue viability in patients with prior myocardial infarction (MI). METHODS AND RESULTS: 82Rb perfusion images were interpreted to identify reversible or irreversible defects, followed by determination of their 18F-fluorodeoxyglucose (18F-FDG) uptake pattern. In 155 patients with prior MI, analysis of 613 abnormal segments showed reversible perfusion defects in 13%. The 87% irreversible defects, 18% showed perfusion-metabolism mismatch, whereas 69% showed the match pattern. Reversible perfusion defects and perfusion-metabolism mismatches were noted in 20% (31/155) and 29% (45/155) of patients, respectively, whereas the match pattern was noted in 51% (79/155) of patients. CONCLUSION: Irreversible perfusion defects were common in our patients with prior MI, and distinction between viable and nonviable tissue was not possible by perfusion imaging alone. The identification of hibernating myocardium was possible only with the additional 18F-FDG imaging in about one third of patients. This indicates a significant clinical demand for 18F-FDG imaging that identifies patients who will benefit from revascularization.