Publications by authors named "Xiaoguang Dou"

50 Publications

Long non-coding RNA RP4-694A7.2 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the Regulation of PSAT1.

J Cancer 2021 25;12(18):5633-5643. Epub 2021 Jul 25.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39, Huaxiang Road, Shenyang Liaoning province, China.

Long noncoding RNAs (lncRNAs) have emerged as gene regulators in various cancers, including hepatocellular carcinoma (HCC). However, the biological roles and mechanisms of many lncRNAs in HCC tumorigenesis remain unknown. To identify novel lncRNAs associated with proliferation and metastasis in HCC. Expression profiles of lncRNAs were analyzed in HCC using two GSE datasets (GSE94660 and GSE104310). Functional studies were performed, including cell proliferation, colony formation, wound healing, and Transwell assays. Fluorescence in-situ hybridization (FISH), tandem mass tag (TMT) analyses, parallel reaction monitoring (PRM), and rescue assays were performed to evaluate the mechanisms underlying the effects of RP4-694A7.2. RP4-694A7.2 levels were higher in HCC tissues than in normal liver tissues in published GSE datasets and were elevated in HCC cell lines. Cell function assays revealed that RP4-694A7.2 promotes cell proliferation, invasion, and migration. Furthermore, RP4-694A7.2 was primarily found to be located in the cytoplasm by FISH assay. Then, TMT assay was performed to predict proteins associated with RP4-694A7.2, and 28 cytoplastic proteins were identified by PRM. Finally, phosphoserine aminotransferase 1 (PSAT1) was found to be regulated by RP4-694A7.2 to modulate growth and metastasis in HCC cells using a rescue assay. These results suggested that RP4-694A7.2 promotes HCC cell proliferation and metastasis via PSAT1, providing a candidate therapeutic target for further research.
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http://dx.doi.org/10.7150/jca.59348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364640PMC
July 2021

Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 08 22;54(3):329-338. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
August 2021

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

J Hepatol 2021 Aug 19;75(2):454-461. Epub 2021 May 19.

Department of Infectious Diseases, Guizhou Provincial People's Hospital, Guiyang 550002, China.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.
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http://dx.doi.org/10.1016/j.jhep.2021.05.003DOI Listing
August 2021

STAT6 up-regulation amplifies M2 macrophage anti-inflammatory capacity through mesenchymal stem cells.

Int Immunopharmacol 2021 Feb 13;91:107266. Epub 2020 Dec 13.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China. Electronic address:

Extensive infiltration of M2 macrophages plays a crucial role in repairing acute liver failure (ALF), however, the molecular pathways whereby mesenchymal stem cells (MSCs) induce M2 macrophage polarization remains unknown. We investigated the molecular pathways involved in MSC-induced M2 polarization and describe the potential therapeutic effects of M2 macrophages on ALF. The expression of M2 macrophage markers was significantly increased after M0 macrophages were co-cultured with MSCs in vitro. MSCs induced M2 macrophage polarization by activating STAT6, whereas a STAT6 inhibitor significantly inhibited the expression of M2 macrophage polarization markers (IL-4, CD163, TGF-β, IL-10 and Arg-1). Finally, M2 macrophages significantly reduced the secretion of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from injured hepatocytes. These results demonstrated that MSCs induced M2 macrophage polarization by activating STAT6, and that M2 macrophages increased the expression of anti-inflammatory factors to alleviate ALF.
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http://dx.doi.org/10.1016/j.intimp.2020.107266DOI Listing
February 2021

Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study.

Antivir Ther 2020 ;25(6):293-304

Bristol-Myers Squibb, Shanghai, China.

Background: In China, the optimal management of individuals living with chronic HBV infection (CHB) remains an unmet need. The EVOLVE Study was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naive CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies.

Methods: Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or hepatitis B e antigen (HBeAg) status were enrolled from tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virological response (HBV DNA <300 copies/ml) and HBV disease progression.

Results: Of the 3,408 patients enrolled, 1,807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based versus ETV group (25.9% versus 13.7%); viral breakthrough was the most common reason in the LAM-based group versus financial reasons in the ETV group. At week 240, the virological response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% versus 2.1%) and genotypic resistance (10.1% versus 1.2%; P<0.0001 for both); significantly lower risk of HBV disease progression (14.0% versus 10.7%; P=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% versus 6.4%) and hepatocellular carcinoma (1.9% versus 0.8%).

Conclusions: This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough and resistance with ETV versus LAM-based therapy. ClinicalTrials.gov NCT01726439.
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http://dx.doi.org/10.3851/IMP3372DOI Listing
January 2020

Editorial: serum HBV RNA biphasic decline in patients with HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues.

Aliment Pharmacol Ther 2020 09;52(5):881-882

Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.

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http://dx.doi.org/10.1111/apt.15975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496356PMC
September 2020

Controlled attenuation parameter value-based diagnostic algorithm improves the accuracy of liver stiffness measurement in chronic hepatitis B patients.

Aging (Albany NY) 2020 08 24;12(16):16072-16082. Epub 2020 Aug 24.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang Liaoning Province, China.

Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis because of steatosis. However, the impact of the controlled attenuation parameter (CAP) on liver stiffness cutoff values remains unknown; CAP was used to quantify and diagnose the severity of hepatic steatosis. The study was conducted to determine the effect of CAP on liver stiffness cutoff values in chronic hepatitis B (CHB) patients. A retrospective cross-sectional study was performed in liver biopsy-proven CHB patients. The median LSM (kPa) in the elevated CAP group was higher than that in the normal CAP group at the same fibrosis stage. For S2-4, the area under the receiver operating characteristic (AUROC) curve of LSM was 0.78 and 0.72 in the normal and elevated CAP groups, respectively. When a cutoff value of 8.9 kPa was used, the diagnostic accuracy was 77.82% and 63.41% in the normal and elevated CAP groups, respectively. Compared with the alanine transaminase (ALT)-based LSM algorithm, the CAP-based LSM algorithm had a similar correct diagnosis rate (33.64% vs. 33.94%, respectively) but a lower misdiagnosis rate (16.97% vs. 20.30%, respectively). The new CAP-based LSM diagnostic algorithm will improve the diagnostic accuracy of liver fibrosis in CHB patients.
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http://dx.doi.org/10.18632/aging.103522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485708PMC
August 2020

aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis.

J Hepatol 2020 12 21;73(6):1368-1378. Epub 2020 Jul 21.

Department of Infectious Diseases, First Hospital of Shanxi Medical University, Taiyuan, China.

Background & Aims: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis.

Methods: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686).

Results: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%.

Conclusions: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide.

Lay Summary: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.
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http://dx.doi.org/10.1016/j.jhep.2020.07.025DOI Listing
December 2020

Utility of Transabdominal Ultrasonography Enhanced by Oral Cellulose-Based Contrast Agent in Depicting Varices at Cardia and Fundus.

Ultrasound Med Biol 2020 06 23;46(6):1428-1434. Epub 2020 Mar 23.

Gastroenterology Department, Shengjing Hospital of China Medical University, Liaoning Province, People's Republic of China. Electronic address:

The use of transabdominal color Doppler ultrasound after oral administration of an oral cellulose-based contrast agent (TUS-OCCA) in depicting varices at the cardia and fundus was explored. Both gastroscopy and transabdominal color Doppler ultrasound (TUS) were performed for this purpose, with gastroscopy serving as the gold standard. Patients were assigned by TUS protocol to one of three groups: TUS + empty stomach (TUS-ES); TUS + oral water intake (TUS-OW); and TUS-OCCA. TUS-based grading of varices reflected venous diameters and blood flow velocities, designated as follows: Ux = difficulty discerning gastric fundus and cardia or delineating varices; U0 = no detectable varices; U1 = diameter <5 mm, flow rate <10 cm/s; U2 = diameter <5 mm, flow rate ≥10 cm/s; U3 = diameter 5-10 mm, flow rate <10 cm/s; U4 = diameter 5-10 mm, flow rate ≥10 cm/s; and U5 = diameter >10 mm, any flow rate. Between August 2016 and August 2019, 239 patients with cirrhosis were enrolled prospectively, including bleeding (n = 71) and non-bleeding (n = 168) groups. Varices were directly observed in 10.5% (25/239) of TUS-ES group members, compared with 59.2% (58/98) of the TUS-OW group and 89.6% (104/116) of the TUS-OCCA group; all detection rates differed significantly (TUS-OCCA > TUS-OW > TUS-ES, p < 0.05). TUS-based grading (as defined) revealed the following patient distribution: Ux, n = 34; U0, n = 18; U1, n = 50; U2, n = 41; U3, n = 16; U4, n = 46; U5, n = 34. In grading by variceal diameter, overall correspondence between TUS and gastroscopy was 93% (174/187). TUS-OCCA greatly improved rates of detection of varices at the cardia and fundus, offering a new method by which diagnosis and quantitative grading may be achieved and affording an excellent, non-invasive approach to dynamic follow-up.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.02.011DOI Listing
June 2020

HBV DNA and HBsAg: Early Prediction of Response to Peginterferon α-2a in HBeAg-Negative Chronic Hepatitis B.

Int J Med Sci 2020 4;17(3):383-389. Epub 2020 Feb 4.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, 110022, China.

: The proportion of hepatitis e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients in China has increased rapidly. However, the response of these patients to peginterferon (peg-IFN) treatment is poor, and the antiviral treatment strategies are inconsistent. This study aimed to investigate the role of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) in early prediction of response in HBeAg-negative CHB patients receiving peg-IFN α-2a. : Treatment-naïve HBeAg-negative patients were involved in this prospective study during 2014-2018. The HBV DNA and HBsAg were quantified at baseline and during treatment (weeks 12, 24 and 48) in sera. The factors associated with HBV DNA undetectable and HBsAg <100 IU/ml at treatment 48 weeks were assessed. : This study involved 45 patients. There was HBV DNA undetectable in 36 cases (80%), including 19 (52.8%) with HBsAg <100 IU/ml at week 48. The HBV DNA <2.0 logIU/ml at week 24 (PPV = 96.9%, NPV = 66.7%, = 0.018) was an independent predictor of HBV DNA undetectable at week 48. The HBsAg <800 IU/ml at baseline (PPV = 92.1%, NPV = 69.7%, = 0.054) and HBsAg decline >5.00-fold at week 24 (PPV = 83.3%, NPV = 77.8%, = 0.038) were independent predictors of HBsAg <100 IU/ml and HBV DNA undetectable at week 48. : Early on-treatment quantification of HBV DNA and HBsAg in patients with HBeAg-negative CHB treated with peg-IFN α-2a may help identify those likely to be cured by this method and optimize therapy strategies.
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http://dx.doi.org/10.7150/ijms.39775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053355PMC
January 2021

Baseline Characteristics and Treatment Patterns of the Patients Recruited to the China Registry of Hepatitis B.

J Clin Transl Hepatol 2019 Dec 20;7(4):322-328. Epub 2019 Dec 20.

Department of Infectious Diseases, Xinjiang Changji Prefecture People's Hospital, Changji, Xinjiang, China.

Chronic hepatitis B virus (HBV) infection remains a major public health problem globally. Here, we describe the baseline characteristics and treatment profiles of HBV-infected patients recruited to the China Registry of Hepatitis B. Inclusion criteria were patients with different stages of chronic HBV infection and complete key data. Exclusion criteria were patients with hepatocellular carcinoma. The baseline clinical, laboratory and treatment profiles were analyzed. Finally, 40,431 patients were included. The median age was 43 years, with 65.2% being men and 51.3% being positive for hepatitis B e antigen (HBeAg). The most common initial diagnosis was chronic hepatitis B (81.0%), followed by cirrhosis (9.3%), inactive carrier of hepatitis B surface antigen (HBsAg) (6.7%), and immune tolerant phase of hepatitis B infection (3.0%). Among the 21,228 patients who were on treatment, 88.0%, 10.0% and 2.0% received nucleos(t)ide analogues (NAs), interferon or combination of NAs and interferon, respectively. The proportion of patients who received preferred NAs (entecavir or tenofovir disoproxil fumarate) had increased from 13.5% in 2003 to 79.7% in 2016. We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study. About half of the patients were HBeAg-positive. NAs were the most commonly used therapy, and use of the preferred NAs had steadily increased in the past decade.
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http://dx.doi.org/10.14218/JCTH.2019.00052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943209PMC
December 2019

Characteristics of Drug-Induced Liver Injury in Northeast China: Disease Spectrum and Drug Types.

Dig Dis Sci 2020 11 6;65(11):3360-3368. Epub 2020 Jan 6.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang City, 110022, Liaoning Province, China.

Background: The aim of this study was to determine the disease spectrum and drug types causing drug-induced liver injury (DILI) in northeast China, so that the affected population can be reminded of the need to increase their post-medication monitoring.

Methods: A total of 470 DILI patients hospitalized at Shengjing Hospital between 2013 and 2016 were involved in this retrospective study.

Results: There were significant differences in the disease spectrum of the different age groups (P < 0.001) and genders (P = 0.009). Drugs used to treat osteopathies, dermatitis and infections, as well as health care supplements, each accounted for > 10% of all drugs that caused DILI. The percentage of DILIs related to Chinese herbal medicines (CHMs) gradually increased with patient age (P = 0.002). The percentage of males taking health supplements or CHMs was significantly lower compared with females. Total bilirubin (β = 0.01, OR = 1.01, P < 0.001) and INR (β = 0.74, OR = 2.11, P < 0.001) were found to be independent predictors of liver damage.

Conclusions: The main type of drug that causes DILI in northeast China is a CHM. There are differences in the disease spectrum found in DILI patients of different ages and gender. Making appropriate changes in the drug-taking habits of high-risk groups and the drugs used to treat high-risk underlying diseases, as well as increasing patient monitoring, may help to reduce the incidence of DILIs.
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http://dx.doi.org/10.1007/s10620-019-06030-6DOI Listing
November 2020

The Prevalence of HBV Infection: A Retrospective Study of 13 Years in a Public Hospital of Northeast China.

Viral Immunol 2020 03 13;33(2):99-104. Epub 2019 Dec 13.

Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang, P.R. China.

The prevalence of hepatitis B virus (HBV) infection was an imbalance in different provinces of China. This study aimed to investigate the prevalence of HBV infection and evaluate the prophylactic measures in a public hospital of northeast China over the preceding 13 years. A total of 13,948 patients in 2004 and 15,256 patients in 2017 of Shengjing Hospital of China Medical University were tested of serum HBsAg, HBeAg, HBsAb, HBeAb, and HBcAb levels with Abbott MEIA Kits. In people born before 1992, HBsAg-positive rate was 5.45% and 6.47%; isolated HBsAb positive rate was 14.62% and 21.24%; HBV marker negative rate was 54.27% and 42.77% in 2004 and 2017 survey, respectively. The males had a significant higher HBsAg-positive rate than the females. In people born during 1992-2004, HBsAg positive rate was 0.58% and 0.57%, isolated HBsAb positive rate was 41.47% and 46.57%; and HBV marker negative rate was 51.97% and 46.86% in 2004 and 2017 survey, respectively. Males and females had no difference of HBsAg-positive rate. In children born after 2005, HBsAg positive rate was 0.11%, isolated HBsAb positive rate was 76.68%, and HBV marker negative rate was 18.51% in 2017 survey. No difference of HBsAg-positive rate was found between the genders. A dramatic decrease of HBsAg positive rate and a progressive increase of HBsAb-positive rate were found among people born after 1992 and progressed further in those born after 2005. Immunization of infants and timely birth dose was the key method for prevention of HBV infection. Expanded HB vaccination would be needed for people born before 2005, especially those born between 1992 and 2004.
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http://dx.doi.org/10.1089/vim.2019.0104DOI Listing
March 2020

A Potential Functional Cure in Chinese HBeAg-negative Chronic Hepatitis B Patients Treated with Peg-interferon Alpha-2a.

J Clin Transl Hepatol 2019 Sep 20;7(3):249-257. Epub 2019 Aug 20.

Department of Liver Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice. In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg. At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%. Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China. ClinicalTrials.gov (NCT01730508).
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http://dx.doi.org/10.14218/JCTH.2019.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783682PMC
September 2019

Sequential combination therapy with interferon, interleukin-2 and therapeutic vaccine in entecavir-suppressed chronic hepatitis B patients: the Endeavor study.

Hepatol Int 2019 Sep 6;13(5):573-586. Epub 2019 Jun 6.

Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, China.

Background: Switching from nucleos(t)ide analogues to interferon (IFN) improves hepatitis B surface antigen (HBsAg) loss. We aimed to evaluate whether combining immunomodulators such as interleukin-2 (IL-2) and therapeutic vaccine with IFN enhances HBsAg loss in entecavir (ETV)-suppressed patients.

Methods: Ninety-four patients exhibiting virological suppression and hepatitis B e antigen (HBeAg) loss following ETV treatment were randomized 1:1:1 to receive ETV (group I) or IFN (group II) for 48 weeks, or IFN and vaccine for 48 weeks plus IL-2 for 12 weeks (group III). The primary endpoint was HBsAg loss at week 48. Peripheral natural killer (NK) cells and regulatory T cells (Treg) were measured as immune checkpoint indicators.

Results: Mean HBsAg decline at week 48 was significantly greater in group III (0.85 log 10 IU/mL) and group II (0.74 log 10 IU/mL), than in group I (0.13 log 10 IU/mL). At week 48, 9.38%, 3.03%, and 3.70% of subjects in group III, II, and I, respectively, achieved HBsAg loss. Among patients with baseline HBsAg titers ranging from 100 to 1500 IU/mL, HBsAg loss rate was 27.3, 7.1, and 0% in group III, II, and I, respectively. Responders in group III showed a significantly higher increase in CD56 CD16NK cells from week 24 to 36, and a significant decline in Treg from week 12 to 24 than non-responders.

Conclusion: For ETV-suppressed patients, particularly those with low baseline HBsAg levels, combination therapy with IFN and other immunomodulators may enhance HBsAg loss, while successful response correlates with partial restoration of NK cells and Tregs.
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http://dx.doi.org/10.1007/s12072-019-09956-1DOI Listing
September 2019

Incidence and Etiology of Drug-Induced Liver Injury in Mainland China.

Gastroenterology 2019 06 8;156(8):2230-2241.e11. Epub 2019 Feb 8.

Shanghai Liver Diseases Research Center, 85th Hospital of Nanjing Military Command, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background & Aims: We performed a nationwide, retrospective study to determine the incidence and causes of drug-induced liver injury (DILI) in mainland China.

Methods: We collected data on a total of 25,927 confirmed DILI cases, hospitalized from 2012 through 2014 at 308 medical centers in mainland China. We collected demographic, medical history, treatment, laboratory, disease severity, and mortality data from all patients. Investigators at each site were asked to complete causality assessments for each case whose diagnosis at discharge was DILI (n = 29,478) according to the Roussel Uclaf Causality Assessment Method.

Results: Most cases of DILI presented with hepatocellular injury (51.39%; 95% confidence interval [CI] 50.76-52.03), followed by mixed injury (28.30%; 95% CI 27.73-28.87) and cholestatic injury (20.31%; 95% CI 19.80-20.82). The leading single classes of implicated drugs were traditional Chinese medicines or herbal and dietary supplements (26.81%) and antituberculosis medications (21.99%). Chronic DILI occurred in 13.00% of the cases and, although 44.40% of the hepatocellular DILI cases fulfilled Hy's Law criteria, only 280 cases (1.08%) progressed to hepatic failure, 2 cases underwent liver transplantation (0.01%), and 102 patients died (0.39%). Among deaths, DILI was judged to have a primary role in 72 (70.59%), a contributory role in 21 (20.59%), and no role in 9 (8.82%). Assuming the proportion of DILI in the entire hospitalized population of China was represented by that observed in the 66 centers where DILI capture was complete, we estimated the annual incidence in the general population to be 23.80 per 100,000 persons (95% CI 20.86-26.74). Only hospitalized patients were included in this analysis, so the true incidence is likely to be higher.

Conclusions: In a retrospective study to determine the incidence and causes of DILI in mainland China, the annual incidence in the general population was estimated to be 23.80 per 100,000 persons; higher than that reported from Western countries. Traditional Chinese medicines, herbal and dietary supplements, and antituberculosis drugs were the leading causes of DILI in mainland China.
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http://dx.doi.org/10.1053/j.gastro.2019.02.002DOI Listing
June 2019

Identification of a role for serum aldo-keto reductase family 1 member B10 in early detection of hepatocellular carcinoma.

Oncol Lett 2018 Dec 3;16(6):7123-7130. Epub 2018 Oct 3.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110022, P.R. China.

Despite improved screening programs, the vast majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. A lack of effective diagnosis methods for preclinical HCC has resulted in a low rate of early detection. Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with several cancer types. However, to the best of our knowledge, the diagnostic value of AKR1B10 in early stage HCC is poorly understood. In the current study, the diagnostic performance of serum AKR1B10 in hepatitis B virus/hepatitis C virus (HBV/HCV)-related liver disorders was evaluated and the unique role of AKR1B10 in diagnosing HCC was assessed. Serum AKR1B10 was detected by sandwich ELISA in 84 patients with HBV/HCV-related HCC, 74 patients with liver cirrhosis, 29 patients with chronic hepatitis and 30 healthy controls. Serum AKR1B10 and α-fetoprotein (AFP) levels were analyzed and compared. Elevated levels of serum AKR1B10 were identified in patients with HCC compared with patients with other liver disorders (P<0.05). Compared with advanced and terminal stage HCC, a significant increase in AKR1B10 levels was primarily detected in early and intermediate stage HCC. The sensitivity (81.0%) and specificity (60.9%) for HCC diagnosis with AKR1B10 were high at a cutoff value of 1.51 ng/ml. Conversely, a prominent increase in AFP was observed in advanced and terminal stage HCC. Furthermore, concurrent measurement of serum AKR1B10 and AFP significantly increased sensitivity and negative predictive value for HCC diagnosis. The results presented in the current study strongly indicate AKR1B10 has a unique role as a biomarker for early stage HBV/HCV-related HCC. Compared with AFP alone, a combination of serum AKR1B10 and AFP increased the diagnostic performance in patients with HCC. In summary, the current results identify a unique role of AKR1B10 in HCC diagnosis.
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http://dx.doi.org/10.3892/ol.2018.9547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256343PMC
December 2018

Immunohistochemistry Detects Increased Expression of Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) in Early-Stage Hepatocellular Carcinoma.

Med Sci Monit 2018 Oct 17;24:7414-7423. Epub 2018 Oct 17.

Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China (mainland).

BACKGROUND Hepatocellular carcinoma (HCC) remains difficult to diagnose at an early stage. Aldo-keto reductase family 1 member B10 (AKR1B10) is an oxidoreductase that is upregulated in some chronic liver diseases. The aim of this study was to use immunohistochemistry to evaluate the expression of AKR1B10 in liver tissue from patients with HCC of different stages. MATERIAL AND METHODS Forty-four patients with a tissue diagnosis of HCC (35 males and 9 females) with 37 control samples of liver tissue containing liver cirrhosis were studied using immunohistochemistry for the expression of AKR1B10. Histological examination determined the grade of HCC; the stage of HCC was determined according to the Barcelona Clinic Liver Cancer (BCLC) staging system. Serum alpha-fetoprotein (AFP) levels were measured and compared between the patients with HCC. RESULTS Immunohistochemistry showed increased expression of AKR1B10 in moderately-differentiated HCC compared with well-differentiated HCC, poorly-differentiated HCC, and liver cirrhosis (P<0.05). Sensitivity and specificity of AKR1B10 expression in HCC were high at a cutoff integral optical density (IOD) value of 89.5. A significant increase in AKR1B10 expression was found in early-stage HCC (P<0.05). Serum AFP levels were increased in patients with poorly-differentiated HCC, were increased in intermediate-stage HCC, and were significantly increased in advanced-stage HCC (P<0.05). CONCLUSIONS Immunohistochemistry showed that the expression of AKR1B10 was increased in tumor tissue from patients with early-stage HCC. Further studies are needed to determine the role of AKR1B10 in the early detection of HCC.
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http://dx.doi.org/10.12659/MSM.910738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201704PMC
October 2018

Management Algorithm for Interrupting Mother-to-Child Transmission of Hepatitis B Virus.

Clin Gastroenterol Hepatol 2019 09 9;17(10):1929-1936.e1. Epub 2018 Oct 9.

School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

In areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Four aspects (screening, antiviral intervention during pregnancy, immunoprophylaxis, and postvaccination serologic testing) are the core components of preventing MTCT. Although the combination of passive and active immunization in newborns of hepatitis B surface antigen-positive mothers reduces MTCT of HBV, this immunoprophylaxis cannot completely eradicate MTCT. In the past decade, administration of antiviral agents to pregnant women has been shown to be safe and effective in reducing MTCT of HBV in combination with immunoprophylaxis. Aiming to achieve zero MTCT, this algorithm recommends the use of antivirals during pregnancy by women with high viral loads. Preventing MTCT is key to achieving the goal of eliminating HBV as a public health threat by 2030. Implementation and enhancement of the standardized algorithm for pregnant women with chronic HBV infection and their infants is urgently needed to prevent MTCT.
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http://dx.doi.org/10.1016/j.cgh.2018.10.007DOI Listing
September 2019

Efficacy and safety of nucleos(t)ide analogues to prevent hepatitis B virus mother-to-child transmission in pregnant women with high viremia: real life practice from China.

Int J Med Sci 2018 22;15(8):796-801. Epub 2018 May 22.

Department of Infectious Disease, Shengjing Hospital, China Medical University, Shenyang 110022, China.

To evaluate the efficacy and safety of nucleos(t)ide analogues, especially telbivudine (LdT) for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in women with high viremia. We conducted a prospective, open-label, multicenter study of LdT for treating pregnant women having high viral loads of hepatitis B virus (HBV DNA>5 log IU/mL) but normal levels of alanine aminotransferase (ALT). Maternal HBV DNA, HBV serologic status and ALT were measured at baseline, 4 weeks after therapy, before delivery, 4 weeks after delivery, and 12 weeks after delivery. Infant HBV serologic status and HBV DNA levels were measured at 7 months. We calculated the MTCT rate of LdT-treated and LdT-untreated groups and analyzed the efficacy and safety of LdT. Ninety-one women (the treatment group) were treated with LdT, and twenty-one patients (the observation group) did not undergo antiviral therapy. The baseline HBV DNA levels were 8.15±0.82 log IU/mL in the treatment group, and 8.09±1.04 log IU/mL in the observation group. The MTCT rate was 0% in the treatment group, and 9.5% in the observation group (p=0.042). In the treatment group, HBV DNA levels were 5.02±0.74 log IU/mL at one month after therapy, and 3.95±0.94 log IU/mL before delivery. Both groups had significant differences from baseline levels in HBV DNA levels (p<0.001). In total, five patients had elevated ALT levels but without evidence of decompensate liver function. No severe adverse events or complications were observed in women or infants. For pregnant women with HBV DNA greater than 5 logIU/mL, LdT therapy was effective in reducing HBV MTCT. If serum HBV DNA was detectable at delivery, discontinuation of LdT immediately was found to be safe and rarely induced off-treatment hepatitis flare.
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http://dx.doi.org/10.7150/ijms.25047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036077PMC
December 2018

Serum Monocyte Chemoattractant Protein-1 Predicts Liver Inflammation of Patients with Chronic Hepatitis B.

Clin Lab 2018 May;64(5):841-846

Background: The usefulness of serum markers for predicting liver necroinflammation is limited in chronic hepatitis B (CHB) patients with normal or slightly elevated alanine aminotransferase (ALT). Monocyte chemoattractant protein-1 (MCP-1) is an important inflammatory mediator in liver disease. Our study was to investigate the expression of MCP-1 and its diagnostic value in patients with HBV-related liver necroinflammation.

Methods: One hundred and six patients with hepatitis B virus (HBV) infection were recruited. All were positive for hepatitis B e antigen (HBeAg) and underwent liver biopsy. Significant inflammation was defined as inflammatory grade ≥ 2 according to Scheuer's classification scoring system. Enzyme-linked immunosorbent assay (ELISA) was used to detect expression of MCP-1 in the peripheral blood of all patients, and receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of MCP-1 and liver inflammation.

Results: MCP-1 level in patients with HBV infection was higher than in healthy controls (p < 0.05). Moreover, MCP-1 level in the ALT ≥ two times of upper limits of normal (2 ULN) group was higher than that of the ALT < 2 ULN group (p < 0.05). In the ALT < 2 ULN group, the MCP-1 level in patients whose inflammatory activity was grade ≥ 2 was higher than in patients with grade < 2 (p < 0.05). ROC curve analysis showed that the area under the curve of MCP-1 in diagnosis of liver inflammation was 0.842.

Conclusions: MCP-1 could be used as a serological marker for non-invasive evaluation of liver inflammation in CHB patients with normal or slightly elevated ALT.
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http://dx.doi.org/10.7754/Clin.Lab.2017.171218DOI Listing
May 2018

China Registry of Hepatitis B (CR-HepB): Protocol and implementation of a nationwide hospital-based registry of hepatitis B.

Scand J Public Health 2020 Mar 1;48(2):233-239. Epub 2018 May 1.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center for Digestive Diseases, China.

The disease burden of chronic HBV infection in China remains high, although the rate of new infections has become extremely low. To facilitate real-world clinical study of chronic HBV infection, we established a nationwide hospital-based electronic platform, named the China Registry of Hepatitis B (CR-HepB). This internet-based registry for chronic hepatitis B recruited patients from tertiary or secondary hospitals that have particular interest and expertise in managing hepatitis B patients. The main inclusion criteria for the database were men or women with hepatitis B surface antigen positivity ≥ 6 months, hepatitis B e antigen positive or negative, with or without cirrhosis, and with or without treatment. At the first time of data entry, demographics, medical history, virology, biochemistry, hematology and radiology reports, as well as diagnosis and treatment information, are recorded. Registered patients then receive a standard of care and follow-up every three (optional) to six months (required) for changes in virology, biochemistry and radiology, as well as clinical progression. ClinicalTrials.gov ID: NCT03108794.
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http://dx.doi.org/10.1177/1403494818772188DOI Listing
March 2020

HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog: New Switch Study.

J Clin Transl Hepatol 2018 Mar 17;6(1):25-34. Epub 2018 Mar 17.

Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 ( = 153) or 96 weeks ( = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
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http://dx.doi.org/10.14218/JCTH.2017.00072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862996PMC
March 2018

Consensus on Pegylated Interferon Alpha in Treatment of Chronic Hepatitis B.

J Clin Transl Hepatol 2018 Mar 17;6(1):1-10. Epub 2018 Mar 17.

The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

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http://dx.doi.org/10.14218/JCTH.2017.00073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862993PMC
March 2018

Sofosbuvir plus ribavirin with or without peginterferon for the treatment of hepatitis C virus: Results from a phase 3b study in China.

J Gastroenterol Hepatol 2018 Jun 25;33(6):1168-1176. Epub 2018 Mar 25.

Gilead Sciences, Inc., Foster City, CA, USA.

Background And Aim: Sofosbuvir is a nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study evaluated the safety and efficacy of sofosbuvir + ribavirin ± peginterferon in Chinese patients infected with HCV genotype 1, 2, 3, or 6.

Methods: Patients with genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12 or 24 weeks, respectively. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR12).

Results: Of 389 patients, 42% had genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male, 58% were treatment-naïve, and 15% had cirrhosis. SVR12 rates for patients receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95% confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%) for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24 weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83-97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events. Three (< 1%) discontinued treatment because of adverse events, of whom one died because of treatment-unrelated adverse events.

Conclusions: Sofosbuvir-based regimens were highly effective and safe in Chinese patients with HCV genotype 1, 2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment in China irrespective of genotype.
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http://dx.doi.org/10.1111/jgh.14102DOI Listing
June 2018

Real-world evidence for nucleoside/nucleotide analogues in a 5-year multicentre study of antiviral-naive chronic hepatitis B patients in China: 52-week results.

Antivir Ther 2018 ;23(3):201-209

Bristol-Myers Squibb, Shanghai, China.

Background: In China, the clinical management of chronic hepatitis B (CHB) is complicated by the use of variousnucleoside/nucleotide analogue (NUC) regimens in treatment-naive patients, including NUCs with low genetic barriers to resistance, with/without add-on therapy and de novo NUC combinations. This longitudinal observational study therefore investigated the real-world clinical management and efficacy of NUC therapy in treatment-naive CHB patients in China.

Methods: Treatment-naive CHB patients initiated on NUC therapy were enrolled from 63 hospitals in tier-2 Chinese cities. Demographic and treatment-specific data were collected, with the objective of reporting real-world treatment patterns and comparing the effectiveness of entecavir (ETV) treatment and lamivudine (LAM)-based treatment. We herein report the first-year data.

Results: 3,408 NUC-naive patients were enrolled and treated with NUCs (53% ETV, 18% LAM-based, 29% other). Overall, 6.6% of patients modified their initial treatment, with ETV having lower rates of treatment modification than other major NUCs (P<0.05). At week 52, the virological response rate was higher with ETV than with LAM-based treatment (77.0% versus 61.4%; P<0.0001). LAM-based treatment was associated with a higher probability of virological breakthrough and genotypic resistance (21.4% and 19.6%, respectively) than ETV (1.6% and 0.1%, respectively; P<0.0001). Treatment-related adverse events or serious adverse events were uncommon.

Conclusions: In this nationwide observational study, more than 50% of patients with CHB in tier-2 city hospitals in China initially received ETV therapy. Consistent with clinical trial results, ETV was more effective than LAM-based treatments in a real-world setting, with the rate of treatment modification being relatively low in ETV-treated patients. ClinicalTrials.gov Identifier: NCT01726439.
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http://dx.doi.org/10.3851/IMP3205DOI Listing
September 2019

HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient.

J Hepatol 2018 04 4;68(4):847-849. Epub 2017 Nov 4.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2017.10.030DOI Listing
April 2018

Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B.

Hepatol Res 2018 Feb 4;48(3):E213-E221. Epub 2017 Oct 4.

Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Aim: The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients.

Methods: Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104.

Results: The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization.

Conclusions: Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization.
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http://dx.doi.org/10.1111/hepr.12972DOI Listing
February 2018

Female gender lost protective effect against disease progression in elderly patients with chronic hepatitis B.

Sci Rep 2016 11 28;6:37498. Epub 2016 Nov 28.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Disease, Beijing, 100050, China.

Female gender and younger age are protective factors against disease progression in chronic hepatitis B (CHB). However, it is not clear whether the disease progression still remains slow in elderly females. This study investigated the interaction of female gender and older age on the development of cirrhosis in patients recorded in China Registry of Hepatitis B. A total of 17,809 CHB patients were enrolled in this multi-center cross-sectional study. The prevalence of cirrhosis in female CHB patients increased faster than that in male CHB patients over 50 years old. Multivariate analysis showed that the increase of adjusted ORs for developing cirrhosis in females started to accelerate after 50 years old: 11.19 (95% CI: 5.93-21.11) in women versus 14.75 (95% CI: 8.35-26.07) in men at ages of 50-59 years, 21.67 (95% CI: 11.05-42.47) versus 24.4 (95% CI: 13.00-45.80) at ages 60-69 years, and 18.78 (95% CI: 6.61-53.36) versus 12.09 (95% CI: 4.35-33.61) in those over 70 years. In conclusion, the protective effect of female gender against cirrhosis gradually lost with increasing age, therefore disease progression should be monitored more closely in elderly women with CHB.
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http://dx.doi.org/10.1038/srep37498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124962PMC
November 2016

A multi-center clinical study comparing Sansure Magb and CAP/CTM HBV tests in the quantitative detection of HBV DNA.

J Infect Dev Ctries 2016 Aug 2;10(7):755-61. Epub 2016 Aug 2.

Xiangya Hospital, Central South University, Changsha, China.

Introduction: As the most reliable means of diagnosing hepatitis (HBV) infection and predicting the prognosis of HBV-related chronic liver disease, the COBAS AmpliPrep/COBAS TaqMan real-time polymerase chain reaction (PCR) (CAP/CTM) assay provides a highly sensitive and accurate method for quantifying HBV DNA. However, the high cost of the COBAS reagents is prohibitive in many developing countries. Thus, we compared the Sansure magnetic bead (Magb) assay, a novel technology developed by a Chinese company, with the CAP/CTM assay.

Methodology: The reproducibility and sensitivity of the Sansure Magb assay were first validated using HBV DNA reference samples. Next, the quantitative results for the two assays using 635 blood samples collected from chronic hepatitis B patients and 10 healthy controls were compared.

Results: The Sansure Magb assay showed high reproducibility and was at least as sensitive and specific as the CAP/CTM assay. Among the patient samples, 407 tested positive by both methods, with 386 (94.84%) showing quantitative differences of less than 1 log unit and 21 (5.16%) showing quantitative differences of between 1 and 2 log units. The results from the assays were closely correlated. Bland-Altman plot analysis showed that only 6.6% of the data points fell outside the 95% limits of agreement, which suggests that the differences between methods are clinically acceptable.

Conclusions: This study demonstrates that the Sansure Magb assay is highly sensitive and reproducible. Based on its reduced cost, the Sansure Magb assay may be more applicable than the CAP/CTM assay for HBV diagnosis in developing countries such as China.
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http://dx.doi.org/10.3855/jidc.7112DOI Listing
August 2016
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