Publications by authors named "Huiying Rao"

53 Publications

Pharmacokinetic bioequivalence, safety, and immunogenicity of GB222, a bevacizumab biosimilar candidate, and bevacizumab in Chinese healthy males: a randomized clinical trial.

Expert Opin Biol Ther 2021 Jul 26:1-10. Epub 2021 Jul 26.

Department of Pharmacy, Peking University People's Hospital, Beijing, China.

Background: This study was conducted to compare the similarity of the pharmacokinetics (PKs), safety, and immunogenicity of GB222, a potential bevacizumab biosimilar, to that of reference bevacizumab in Chinese healthy males.

Research Design And Methods: This was a randomized, double-blind, single-dose, parallel-group clinical trial performed in 84 Chinese healthy males, who were randomly assigned to receive a single infusion dose of 1 mg/kg GB222 or bevacizumab with an 84-days follow-up. The primary endpoint was the area under the plasma concentration-time curve (AUC) from zero to the last quantifiable concentration at time t (AUC). The second endpoints were the safety and immunogenicity evaluation. The PK bioequivalence was verified by the 90% confidence intervals (CIs) of the geometrical mean (GM) ratio for AUC falling within the bioequivalence margin, 80-125%.

Results: The PK profiles of GB222 and bevacizumab were comparable. The 90% CIs of GM ratio of GB222 to bevacizumab for AUC was within the pre-specified bioequivalence margin. The most common treatment-related adverse event was sinus bradycardia. Seventeen subjects (20.2%) tested positive for anti-drug antibodies (ADAs).

Conclusion: GB222 was found to be comparable to bevacizumab in terms of PKs, safety, and immunogenicity for Chinese healthy males.

Trial Registration: ChiCTR-IIR-17,011,143.
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http://dx.doi.org/10.1080/14712598.2021.1954157DOI Listing
July 2021

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

Aliment Pharmacol Ther 2021 Aug 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

Prevention and control measures significantly curbed the SARS-CoV-2 and influenza epidemics in China.

J Virus Erad 2021 Jun 8;7(2):100040. Epub 2021 May 8.

Peking University People's Hospital, National Clinical Research Center for Infectious Disease, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China.

At the end of 2019, an outbreak of pneumonia took place caused by a new coronavirus (SARS-CoV-2 virus), named coronavirus disease 2019 (COVID-19). A series of strict prevention and control measures were then implemented to reduce the spread of the epidemic. Influenza, another respiratory tract virus, may also respond to these measures. To assess the impact of these measures, we used the total number of passengers movement in mainland China from 2018 to 2020 and daily number of railway passenger flow during the 2020 Spring Festival travel rush to reflect the population movement and to analyze newly and cumulatively confirmed COVID-19 and influenza cases. We found that implementing the series of measures against COVID-19 mitigated both COVID-19 and influenza epidemics in China. Prevention and control measures for COVID-19 might be used to control respiratory tract infections to reduce the national health economic burden caused by these pathogens.
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http://dx.doi.org/10.1016/j.jve.2021.100040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106191PMC
June 2021

Incidence and risk factors of hepatocellular carcinoma in patients with hepatitis C in China and the United States.

Sci Rep 2020 12 1;10(1):20922. Epub 2020 Dec 1.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

Hepatitis C virus (HCV) infection is the main cause of hepatocellular carcinoma (HCC) in the United States (US) and an increasingly common cause of HCC in China. We aimed to evaluate the incidence and risk factors of HCC in HCV patients in the US and China. 795 HCV RNA + patients without HCC from University of Michigan Health System (UMHS) in the US and 854 from Peking University Health Sciences Center (PUHSC) in China were prospectively followed for a median of 3.2 and 4.0 years, respectively. 45.4% UMHS and 16.2% PUHSC patients had cirrhosis. 57.6% UMHS and 52.0% PUHSC patients achieved SVR. 45 UMHS and 13 PUHSC patients developed HCC. Cumulative incidence of HCC at 5 years was 7.6% in UMHS and 1.8% in PUHSC cohort (P < 0.001). Ten patients not diagnosed with cirrhosis at enrollment but median APRI ≥ 2.0 developed HCC. Multivariate analysis showed age, gender, cirrhosis and APRI were predictors of HCC while study site and SVR were not. In this study of HCV patients, HCC incidence in the PUHSC cohort was lower than in the UMHS cohort, due to lower proportion of PUHSC patients with cirrhosis. APRI can identify risk of HCC among patients not diagnosed to have cirrhosis.
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http://dx.doi.org/10.1038/s41598-020-77515-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708980PMC
December 2020

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis.

J Clin Transl Hepatol 2020 Sep 11;8(3):255-261. Epub 2020 Sep 11.

Department of Infectious Diseases, Wuhan central hospital, Wuhan, Hubei, China.

Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.
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http://dx.doi.org/10.14218/JCTH.2020.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562795PMC
September 2020

Increasing SARS-CoV-2 nucleic acid testing capacity during the COVID-19 epidemic in Beijing: experience from a general hospital.

Emerg Microbes Infect 2020 Dec;9(1):2358-2360

Trauma Center, Peking University People's Hospital, Beijing, People's Republic of China.

Under the ongoing COVID-19 prevention and control measures in China, increasing the laboratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid testing capacity has become the top priority. Since the COVID-19 outbreak in Xinfadi market in Beijing in June 2020, large-scale screening of key populations has been carried out, challenging the nucleic acid testing capabilities of hospital laboratories. Therefore, within 48 hours, Peking University People's Hospital (PKUPH) transformed a non-nucleic acid testing laboratory into a SARS-CoV-2 nucleic acid testing laboratory. Based on the original structure of the building, we adapted measures to local conditions, sorted out a new testing process, and quickly started testing for COVID-19. The nucleic acid testing process has been optimized, including quality control, personal operating specifications, and the timeliness of the release of LIS results to form closed-loop management. This high-throughput COVID-19 testing optimization process provides a reference model for other countries that are fighting the epidemic.
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http://dx.doi.org/10.1080/22221751.2020.1837016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605315PMC
December 2020

Relationship between insulin-sensitive obesity and retinal microvascular abnormalities.

Ann Palliat Med 2021 Feb 10;10(2):1031-1041. Epub 2020 Sep 10.

Department of Endocrinology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

Background: Obesity and insulin resistance (IR) are risk factors for microvascular disease (MVD). Whether insulin-sensitive obese individuals are at higher risk for MVD is still debated. We aimed to investigate whether insulin-sensitive obesity is associated with retinal microvascular abnormalities.

Methods: This cross-sectional study recruited a total of 8,313 participants (3,604 males and 4,709 females) aged 21 years or older from 13 villages in rural area and 8 communities in urban area in Fujian province in China between 2011 to 2012. Participants were categorized by insulin-sensitive/-resistant and general/ abdominal obese status. IR was defined as homeostasis model assessment of IR >1.99 (75% percentile). Direct ophthalmoscopic examination was used to diagnose MVD, which was defined as the presence of retinal microvascular abnormalities.

Results: Among the older subjects (aged 65-79 years), those who were obese had a markedly higher risk for MVD, both in insulin-sensitive [odds ratio (OR): 2.259, 95% confidence interval (CI): 1.041-4.904, P=0.039] and insulin-resistant (OR: 2.356, 95% CI: 1.064-5.218, P=0.035) individuals. Additionally, insulinsensitive/-resistant abdominal obesity in middle-aged people showed an increased risk for prevalent MVD in women (OR: 2.061, 3.322; 95% CI: 1.004-4.233, 1.645-6.709; P values: 0.049, <0.001).

Conclusions: In this study, obesity was closely related to an elevated higher risk of MVD, regardless of IR, especially in older people and abdominally obese middle-aged women. Obesity may be similar to diabetes mellitus, with chronic complications that not only cause cardiovascular diseases but also MVD. Direct ophthalmoscopy may be a noninvasive and meaningful method of early screening for obesity-related MVD. Insulin-sensitive obesity, like impaired glucose tolerance, is a pre-existing state of insulin resistant obesity.
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http://dx.doi.org/10.21037/apm-20-447DOI Listing
February 2021

Comparison of clinical outcomes and impact of SVR in American and Chinese patients with chronic hepatitis C.

JHEP Rep 2020 Aug 12;2(4):100136. Epub 2020 Jun 12.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.

Background & Aims: Chronic HCV infection is an important cause of hepatocellular carcinoma (HCC) and liver failure in the US but limited data are available in China. We compared the incidence of clinical outcomes among adults with chronic HCV infection in the US and China and examined factors associated with outcomes.

Methods: A parallel prospective study of 2 cohorts of patients with HCV RNA+ recruited in 1 site in the US (UMHS) and 3 sites (PUHSC) in China between September 2011 and July 2015 was carried out. Composite liver outcomes (liver-related deaths, HCC, liver transplantation or liver decompensation), were analysed using competing-risk Cox proportional hazards model to determine incidence and associated factors.

Results: A total of 795 UMHS and 854 PUHSC patients were followed for a median of 3.06 and 3.99 years, respectively. At enrolment, a significantly higher percentage of UMHS patients had cirrhosis (45.4% 16.2%). The 5-year cumulative incidence of composite liver outcomes was significantly higher in UMHS than in PUHSC patients (25.3% 6.6%, <0.0001). Stratification by stage of liver disease at enrolment showed this difference persisted only in the subgroup without cirrhosis due to higher aspartate aminotransferase to platelet ratio index (APRI) in the UMHS cohort. A total of 493 UMHS and 502 PUHSC patients received HCV treatment, and sustained virologic response (SVR) was achieved in 88.0% UMHS and 86.8% PUHSC treated-patients. SVR as time-dependent variable was associated with 80% lower risk of composite liver outcomes among patients with decompensated cirrhosis but not the overall cohorts.

Conclusions: When accounting for disease severity at entry, the incidence of composite liver outcomes was similar in patients with HCV in the US and China. Achievement of SVR had the greatest short-term impact on patients with decompensated cirrhosis.

Lay Summary: Patients with chronic hepatitis C virus infection were recruited from centres in the United States and China. During follow-up, a higher percentage of the American patients had clinical outcomes: liver failure, liver cancer, liver transplant or liver-related deaths than the Chinese patients, mainly because more American patients had cirrhosis at enrolment. Older age and more advanced liver disease were associated with higher incidence of outcomes overall and viral clearance after hepatitis C treatment was associated with a lower incidence of outcomes in patients with advanced cirrhosis. Our findings highlight the importance of improving diagnosis and treatment of hepatitis C before advanced liver disease develops.
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http://dx.doi.org/10.1016/j.jhepr.2020.100136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369613PMC
August 2020

A synonymous mutation in exon 39 of FBN1 causes exon skipping leading to Marfan syndrome.

Genomics 2020 11 17;112(6):3856-3861. Epub 2020 Jun 17.

Department of Clinical Laboratory, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou 350001, China. Electronic address:

Marfan syndrome is a heritable autosomal-dominant connective tissue disorder and it was typically caused by mutations in FBN1. However, the synonymous mutation was seldom recorded to be related to Marfan syndrome. Hereon, Multiplex ligation-dependent probe amplification failed to detect a copy number variant involving FBN1 but a synonymous mutation c.4773A > G (p.Gly1591Gly) was identified by NGS in exon 39. RNA was extracted from patient's aortic tissue and reverse polymerase chain reaction demonstrated the presence of a shortened mRNA transcript. Results of minigene models indicated that c.4773A > G was bona fide responsibility for the aberrant splicing pattern, and artificial mutations of c.4773A > C and c.4773A > T also gave rise to fragments with exon 39 entire skipped. Together, the novel synonymous mutations in c.4773 position (A > G, C, T), middle of exon 39 of FBN1 gene, was found to be associated with Marfan syndrome by altering the splicing pattern of pre-mRNA.
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http://dx.doi.org/10.1016/j.ygeno.2020.06.024DOI Listing
November 2020

A non-canonical role for p27Kip1 in restricting proliferation of corneal endothelial cells during development.

PLoS One 2020 13;15(1):e0226725. Epub 2020 Jan 13.

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States of America.

The cell cycle regulator p27Kip1 is a critical factor controlling cell number in many lineages. While its anti-proliferative effects are well-established, the extent to which this is a result of its function as a cyclin-dependent kinase (CDK) inhibitor or through other known molecular interactions is not clear. To genetically dissect its role in the developing corneal endothelium, we examined mice harboring two loss-of-function alleles, a null allele (p27-) that abrogates all protein function and a knockin allele (p27CK-) that targets only its interaction with cyclins and CDKs. Whole-animal mutants, in which all cells are either homozygous knockout or knockin, exhibit identical proliferative increases (~0.6-fold) compared with wild-type tissues. On the other hand, use of mosaic analysis with double markers (MADM) to produce infrequently-occurring clones of wild-type and mutant cells within the same tissue environment uncovers a roughly three- and six-fold expansion of individual p27CK-/CK- and p27-/- cells, respectively. Mosaicism also reveals distinct migration phenotypes, with p27-/- cells being highly restricted to their site of production and p27CK-/CK- cells more widely scattered within the endothelium. Using a density-based clustering algorithm to quantify dispersal of MADM-generated clones, a four-fold difference in aggregation is seen between the two types of mutant cells. Overall, our analysis reveals that, in developing mouse corneal endothelium, p27 regulates cell number by acting cell autonomously, both through its interactions with cyclins and CDKs and through a cyclin-CDK-independent mechanism(s). Combined with its parallel influence on cell motility, it constitutes a potent multi-functional effector mechanism with major impact on tissue organization.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226725PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957298PMC
April 2020

Fat Accumulation, Liver Fibrosis, and Metabolic Abnormalities in Chinese Patients With Moderate/Severe Versus Mild Hepatic Steatosis.

Hepatol Commun 2019 Dec 7;3(12):1585-1597. Epub 2019 Oct 7.

Division of Gastroenterology and Hepatology University of Michigan Ann Arbor MI.

Several drugs in development for nonalcoholic fatty liver disease (NAFLD) aim to decrease the amount of fat in the liver. We compared quantity and quality of fat in subcutaneous, visceral and muscle compartments, liver fibrosis, and prevalence of metabolic abnormalities between Chinese patients with moderate/severe hepatic steatosis versus those with mild hepatic steatosis. NAFLD patients were prospectively recruited from Peking University People's Hospital in Beijing, China. All patients had baseline body composition measurements using computed tomography and analytic morphomics, clinical evaluation, labs and Fibroscan® controlled attenuation parameter and liver stiffness measurement. Moderate/severe hepatic steatosis was defined as computed tomography liver attenuation of 40 Hounsfield units or less. Calorie intake and physical activity were based on self-report. A total of 160 NAFLD patients were included (46% men, median age 47 years): 50% had normal body mass index (BMI), 24% were diabetic, and 56% had metabolic syndrome (MS). Fifty-three (33%) had moderate/severe steatosis, of whom 19 (35.8%) had normal BMI, and the rest had mild steatosis. Patients who had moderate/severe steatosis had significantly higher BMI, waist circumference, aminotransferases, controlled attenuation parameter, liver stiffness measurement, and prevalence of MS compared to those with mild steatosis. They also had larger visceral fat area, subcutaneous fat area, and low density dorsal muscle area. In addition, their calorie intake was higher and time spent on recreation activities was shorter. : NAFLD patients with moderate/severe steatosis, including those with normal BMI, had higher prevalence of MS and more fat in visceral, subcutaneous, and muscle compartments than those with mild steatosis. They also had more advanced liver disease. Strategies to decrease hepatic fat may benefit both liver and metabolic diseases.
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http://dx.doi.org/10.1002/hep4.1435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887912PMC
December 2019

STING expression in monocyte-derived macrophages is associated with the progression of liver inflammation and fibrosis in patients with nonalcoholic fatty liver disease.

Lab Invest 2020 04 19;100(4):542-552. Epub 2019 Nov 19.

Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, 100044, Beijing, China.

The stimulator of interferon genes (STING) in macrophages plays a crucial role in nonalcoholic fatty liver disease (NAFLD) progression. However, there is a lack of evidence from large samples of patients to validate a deleterious role for STING in NAFLD. Moreover, sources of STING-expressing cells that are related to NAFLD remain to be definitively characterized. To investigate STING expression and explore its correlation with NAFLD progression in human subjects, our study involved liver samples from 98 NAFLD subjects and 8 controls. STING and p-TBK1 expression in nonparenchymal liver cells was analyzed and correlated with NAFLD pathological features. Numbers of STING cells were increased in livers from nonalcoholic steatohepatitis (NASH) patients compared with controls, especially in the liver portal tract of NASH patients with fibrosis (p < 0.05). Moreover, numbers of STING cells in livers of NASH patients were increased with aggravation of inflammation grade and fibrosis stage (p < 0.05). STING was mainly expressed in macrophages, including monocyte-derived macrophages (CCR2, S100A9), Kupffer cells (CD68) and CD163 macrophages. Compared with controls, numbers of STING/CCR2 and STING/S100A9 cells were significantly increased in livers from NASH patients with fibrosis and positively correlated with liver inflammation grade and fibrosis stage (p < 0.05). However, numbers of STING/CD68 and STING/CD163 cells were significantly increased in livers from NASH patients with advanced fibrosis and correlated only with aggravation of fibrosis stage (p < 0.05). Furthermore, compared with controls, NASH patients exhibited significantly increased STING/p-TBK1 cell numbers. In a coculture system, the amount of p-TBK1 and the mRNAs of IL1β and IL6 in THP1 macrophages, as well as the amount of α-SMA and the mRNAs of Col1a1, Fn and TGFβ1 in LX2 cells were significantly increased upon STING activation in macrophages (p < 0.05). Therefore, increased STING expression in MoMFs appears to be indicative of NAFLD progression, and STING could be a new target for NAFLD therapy.
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http://dx.doi.org/10.1038/s41374-019-0342-6DOI Listing
April 2020

Noninvasive Measurements Predict Liver Fibrosis Well in Hepatitis C Virus Patients After Direct-Acting Antiviral Therapy.

Dig Dis Sci 2020 05 25;65(5):1491-1500. Epub 2019 Oct 25.

Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, No. 11 Xizhimen South Street, Beijing, 100044, China.

Background: Short-time usage of direct-acting antiviral agents (DAA) limited knowledge regarding histological outcomes and predictive values of noninvasive measurements in patients with hepatitis C virus (HCV) after sustained virologic response (SVR) with DAA.

Aims: This study aimed to indicate histological changes and assess predictive value of noninvasive measurements for fibrosis in these patients.

Methods: HCV patients who achieved SVR by DAA were identified. Pre- and post-SVR clinical and histological data were collected.

Results: Of patients, 83% (33/40), 38% (15/40) and 83% (33/40) achieved inflammation improvement, fibrosis regression and histological improvement, respectively. Liver stiffness measurements (LSM), APRI, and FIB-4 could predict post-SVR fibrosis well without significant differences. Areas under receiver operating characteristic curves of LSM, APRI, and FIB-4 were 0.78, 0.81, and 0.87 for post-SVR advanced fibrosis (≥ F4) and 0.86, 0.86, and 0.85 for post-SVR cirrhosis (≥ F5), respectively. Pre-SVR LSM, APRI, and FIB-4 values were significantly lower in patients with fibrosis regression (P = 0.003-0.012), while FIB-4 was significantly lower in patients with histological improvement (P = 0.012-0.033). Patients with higher pre-SVR Ishak scores tended to have bigger decline in APRI (P = 0.025) and FIB-4 (P = 0.024) after SVR.

Conclusions: DAA could improve liver inflammation and fibrosis of HCV patients in a short time after SVR. LSM, APRI, and FIB-4 predict fibrosis well even after SVR by DAA. Most of the cutoff values for advanced fibrosis (≥ F4) and cirrhosis (≥ F5) of these noninvasive measurements decreased significantly after SVR, maybe because of the inflammation improvement.
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http://dx.doi.org/10.1007/s10620-019-05886-yDOI Listing
May 2020

Real-world clinical outcomes among individuals with chronic HCV infection in China: CCgenos study.

Antivir Ther 2019 ;24(7):473-483

Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.

Background: This 5-year follow-up of the CCgenos cross-sectional study aimed to observe real-life outcomes in a cohort of 997 Han Chinese patients with chronic HCV infection and to explore the impacts of HCV genotype, patient characteristics and treatment status.

Methods: Clinical information and centralized HCV RNA measures were collected every 6/3 months for untreated/treated patients. Overall disease progression was defined as ≥1 of: de novo development of cirrhosis, Child-Turcotte-Pugh score increased by ≥2 points (if cirrhosis at baseline), progression to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant or death. Cox regression assessed risk factors for the time from estimated infection to cirrhosis or HCC. Logistic regression assessed risk factors for incidence rates of cirrhosis and overall disease progression.

Results: 281 of 514 patients enrolled across China completed 5 years of follow-up. Overall disease progression occurred in 36/364 (9.9%) treated patients and 35/148 (23.6%) untreated patients (odds ratio = 0.35; 95% CI 0.21, 0.59; P<0.0001). Overall disease progression occurred in 6/231 (2.6%) patients achieving sustained virological response at 24 weeks (SVR24) versus 11/82 (13.4%) who did not (P=0.0002). Cirrhosis development was significantly associated with abnormal aspartate aminotransferase (AST), age ≥40 years, body mass index ≥28 kg/m, HCV GT1, platelet count <100×10/l, and AST to platelet ratio index (APRI) ≥2 (multivariate Cox regression, P<0.05). HCC was significantly associated with HCV GT1 and platelet count <100×10/l (multivariate Cox regression, P<0.05).

Conclusions: Achieving SVR24 significantly reduced the probability of overall disease progression but no significant difference was seen for both cirrhosis and HCC during 5 years of follow-up.
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http://dx.doi.org/10.3851/IMP3334DOI Listing
October 2020

Safety and efficacy of coblopasvir and sofosbuvir in patients with genotypes 1, 2, 3 and 6 HCV infections without or with compensated cirrhosis.

J Viral Hepat 2020 01 2;27(1):45-51. Epub 2019 Oct 2.

Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.

A simple, pangenotypic and effective treatment regimen for patients with a broad range of chronic hepatitis C virus (HCV) infections remains an unmet medical need. We conducted a phase 2, randomized, open study involving untreated patients with chronic HCV genotypes 1, 2, 3, or 6 infections. Patients without cirrhosis were randomly assigned in a 1:2 ratio to receive capsules of the NS5A inhibitor coblopasvir at a dose of 30 or 60 mg plus tablets of the nucleotide polymerase inhibitor sofosbuvir (400 mg) once daily for 12 weeks. Patients with cirrhosis received 60 mg coblopasvir plus sofosbuvir for 12 weeks. The primary endpoint was the sustained virologic response at 12 weeks after the end of therapy (SVR12). Of the 110 patients who were enrolled in the study, 59 were male, 62.7% had HCV genotype 1, 24.5% had genotype 2, 6.4% had genotype 3, and 6.4% had genotype 6. The average age was 45.5 years. A total of 10.9% of patients had compensated cirrhosis. The rate of SVR12 was 98.2% in the intention-to-treat (ITT). One genotype 6 patient with cirrhosis experienced virologic relapse. One genotype 2 patient without cirrhosis failed to complete the follow-up and quit the study. Serious adverse events (SAEs) were reported in 2 patients and were not related to coblopasvir and sofosbuvir. Most adverse events (AEs) did not require treatment. Coblopasvir plus sofosbuvir taken once daily for 12 weeks provided high rates of sustained virologic response (SVR) and had a good safety profile among patients with HCV genotypes 1, 2, 3, or 6 infections, including those with compensated cirrhosis.
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http://dx.doi.org/10.1111/jvh.13208DOI Listing
January 2020

Detection of residual HCV-RNA in patients who have achieved sustained virological response is associated with persistent histological abnormality.

EBioMedicine 2019 Aug 23;46:227-235. Epub 2019 Jul 23.

Department of Pathology and Hepatology, the 5th Medical Center, Chinese PLA General Hospital, China. Electronic address:

Background: Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI.

Methods: Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed.

Results: OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment.

Conclusions: HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR.
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http://dx.doi.org/10.1016/j.ebiom.2019.07.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711338PMC
August 2019

Survey of Nonalcoholic Fatty Liver Disease Knowledge, Nutrition, and Physical Activity Patterns Among the General Public in Beijing, China.

Dig Dis Sci 2019 12 4;64(12):3480-3488. Epub 2019 Jul 4.

Division of Gastroenterology and Hepatology, University of Michigan, 1500 E Medical Center Drive, 3912 Taubman Center, SPC 5362, Ann Arbor, MI, 48109, USA.

Background: Despite high prevalence of nonalcoholic fatty liver disease in China, understanding of the disease appears to be low.

Aims: We assessed the knowledge of NAFLD among the public in Beijing, China, as well as diet and physical activity patterns, which may provide information useful for NAFLD prevention and management.

Methods: We surveyed adult patients and family members in the Peking University Health Science Center (PUHSC) ultrasound clinic and office staff in Beijing, China. Participants provided demographic and medical history data. NAFLD-related knowledge and diet and physical activity were assessed.

Results: A total of 1296 participants at the PUHSC clinic (51% female, median age 35, 61% college-educated) and 494 participants in offices (61% female, median age 43, 74% college-educated) completed the survey. Response rate was 68.4% and 96.7%, respectively. In clinic and offices, 44% versus 48% were overweight/obese, 5% had a history of diabetes in both groups, and 14% versus 23% had a personal history of NAFLD. Median knowledge score was 15 out of 25 in clinic versus 16 in offices. 44.9% reported minimal physical activity. Factors associated with higher NAFLD knowledge scores (> 16) on multivariate analysis included college education or higher (OR 1.7, p = 0.01), family history of hyperlipidemia (OR 1.96, p < 0.001), and number of sugary drinks per week (OR 0.74, p = 0.006). No factors were significantly associated with physical activity levels.

Conclusions: Adults in Beijing had low knowledge about NAFLD, and most were not physically active. Programs to increase public awareness of NAFLD and promote physical activity are critical to curb this growing epidemic.
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http://dx.doi.org/10.1007/s10620-019-05709-0DOI Listing
December 2019

Comparison of the efficacy of sofosbuvir plus ribavirin in Chinese patients with genotype 3a or 3b HCV infection.

J Med Virol 2019 07 3;91(7):1313-1318. Epub 2019 Apr 3.

Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Beijing, China.

Background And Aim: Genotype 3b hepatitis C virus (HCV) infection represents approximately 50% of patients with genotype 3 in China. We compared the efficacy of sofosbuvir (SOF) plus ribavirin (RBV) in Chinese patients with genotype 3a and 3b HCV.

Methods: The analyzed data are from a phase 3, open-label study of SOF plus RBV for 24 weeks conducted in China. The primary endpoint for the trial was sustained virologic response at 12 weeks after the end of therapy (SVR12).

Results: Of 126 patients included in this analysis, 58 (46%) had genotype 3a and 68 (54%) had genotype 3b. Both the subtypes were similar in age, sex, body mass index, IL28B, and baseline HCV RNA. However, more treatment-experienced and cirrhotic patients were in the genotype 3b group. All 100% of patients with genotype 3a (95% confidence interval [CI], 94-100), and 91% (95% CI, 82-97) of patients with genotype 3b achieved SVR12 (P = 0.030). For treatment-experienced patients with genotype 3b, the SVR12 rate was 73% (95% CI, 39-94) and 88% (95% CI, 64-99) among patients with and without cirrhosis (P = 1.00), respectively.

Conclusion: SOF plus RBV for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of SVR. However, the SVR12 rate among patients with genotype 3b was lower than that observed in patients with genotype 3a infection, particularly among treatment-experienced patients with cirrhosis.
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http://dx.doi.org/10.1002/jmv.25454DOI Listing
July 2019

Awareness and Knowledge of Nonalcoholic Fatty Liver Disease Among Office Employees in Beijing, China.

Dig Dis Sci 2019 03 27;64(3):708-717. Epub 2018 Nov 27.

Division of Gastroenterology and Hepatology, University of Michigan, 1500 E Medical Center Drive, 3912 Taubman Center, SPC 5362, Ann Arbor, MI, 48109, USA.

Background: Prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing in China; however, awareness and knowledge of NAFLD is lacking among the Chinese public.

Aims: We investigated knowledge about NAFLD and the impact of a brief educational seminar among office employees in Beijing.

Methods: Educational seminar on knowledge about NAFLD and recommendations on diet and physical activity and a pre- and a post-survey in 8 offices in Beijing.

Results: A total of 420 participants (24.7% with a diagnosis of NAFLD) completed both the pre- and post-surveys. Median age was 42, 39.1% were men, 93.9% participants had some college education, 50.5% were overweight/obese, and 74.9% were inactive/minimally active. Only 31.2% had awareness of NAFLD. Median baseline knowledge score (of a total of 25) was 17 in participants with and 16 in those without a diagnosis of NAFLD. After the seminar, 30.9% of participants with and 50.8% without a diagnosis of NAFLD increased their knowledge score by ≥ 3 points, and 92.9% indicated they will improve their diet and physical activity. Multivariate logistic regression analyses found baseline knowledge score was associated with personal diagnosis of NAFLD and family history of dyslipidemia while improvement in knowledge was associated with lower baseline knowledge score and absence of a personal diagnosis of NAFLD.

Conclusion: We found a high prevalence but a low awareness of NAFLD among office employees in Beijing. A brief educational seminar improved knowledge about NAFLD and motivated lifestyle changes. More educational efforts are needed to decrease the burden of NAFLD in China.
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http://dx.doi.org/10.1007/s10620-018-5389-5DOI Listing
March 2019

Is Retinal Microvascular Abnormalities an Independent Risk Factor of Vertebral Fractures? A Prospective Study From a Chinese Population.

JBMR Plus 2017 Oct 10;1(2):107-115. Epub 2017 Oct 10.

Department of Endocrinology Fujian Provincial Hospital Key Laboratory of Endocrinology Fujian Medical University Fuzhou China.

Low bone mineral density (BMD) and microvascular diseases (MVD) share various common risk factors; however, whether MVD is an independent risk factor of vertebral fractures is incompletely understood. The aim of this study is to clarify whether MVD is an independent risk factor of vertebral fractures. In this prospective study, calcaneal BMD and retinal microvascular abnormalities were assessed at baseline from June 2011 to January 2012. A total of 2176 premenopausal women, 2633 postmenopausal women, 2998 men aged <65 years, and 737 men aged ≥65 were included. Then with/without retinal microvascular abnormalities cohorts were followed for an average of 2.93 years to find out the relationship between MVD and vertebral fractures. At the baseline, after full adjustment, retinal microvascular abnormalities were related to risk of low BMD only in men aged ≥65 years (odds ratio [OR] = 2.506; 95% confidence interval [CI] 1.454-4.321;  = 0.001). After follow-up of 2.93 years, retinal microvascular abnormalities were related to risk of vertebral fractures in men aged ≥65 years (OR = 2.475; 95% CI 1.085-5.646;  = 0.031) when adjustment for confounding factors. However, no associations were found between MVD and vertebral fractures in men aged <65 years, premenopausal women, and postmenopausal women. When stratified by diabetes, in the without-diabetes group, the men with retinal microvascular abnormalities had higher risk for vertebral fractures than without retinopathy (OR = 2.194; 95% CI 1.097-4.389;  = 0.026); however, the difference was not found in women. In the diabetes group, there were no significant differences of risk for vertebral fractures between those with retinal microvascular abnormalities and those without both in men and women. Stratified by hypertension, the men with retinopathy had higher risk for vertebral fractures than those without among the hypertension group (OR = 2.034; 95% CI 1.163-3.559;  = 0.013), but a difference was not found among women. In the without-hypertension group, no relation was found between MVD and fracture both in men and women. In conclusion, MVD is an independent risk factor of vertebral fractures in old men. © 2017 The Authors. is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124164PMC
October 2017

Evaluation of an antigen assay for diagnosing acute and chronic hepatitis E genotype 4 infection.

J Gastroenterol Hepatol 2019 Feb 27;34(2):458-465. Epub 2018 Aug 27.

Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.

Background And Aim: Results obtained from different hepatitis E virus (HEV) tests are usually inconsistent. The detection of serum HEV antigen (Ag) has been suggested to be more sensitive for the diagnosis of genotypes 1 and 3 HEV.

Methods: We compared the diagnostic accuracies of serum HEV Ag and HEV RNA by using 202 serum samples from patients suspected acute viral hepatitis.

Results: The HEV Ag assay was 100% specific. The lower detected levels of viremia ranged from 10 to 10  copies/mL. The sensitivity of the HEV Ag test was 90.5%. One of the 42 cases was negative for anti-HEV IgM, but HEV Ag was still detectable. The detectable period of HEV Ag was in concordance with the detectable period of HEV RNA. Serum HEV Ag was persistently detected in two cases of chronic hepatitis E, confirmed by the persistent presence of HEV RNA despite being negative for anti-HEV IgM. HEV Ag demonstrated good consistency with positive HEV RNA (k = 0.938, P < 0.001). Receiver operating characteristic analysis of HEV Ag suggested a second cut-off value of >0.095 to predict HEV patients with 95.24% sensitivity and 98.75% specificity, and the area under the curve was 0.9887, which was higher than that of three commercial anti-HEV IgM ELISA tests.

Conclusions: The presence of HEV Ag has good consistency with HEV RNA in both acute and chronic genotype 4 hepatitis E. HEV Ag is a more promising serum marker to identify active genotype 4 HEV infection than anti-HEV IgM and HEV RNA.
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http://dx.doi.org/10.1111/jgh.14405DOI Listing
February 2019

A cross-sectional assessment of health-related quality of life in Chinese patients with chronic hepatitis c virus infection with EQ-5D.

Health Qual Life Outcomes 2018 Jun 15;16(1):124. Epub 2018 Jun 15.

Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Beijing, China.

Background: Hepatitis C virus (HCV) infection is one of the most common liver infections, with a decrement in HRQoL of HCV patients. This study aims to assess Health-related quality of life (HRQoL) in Chinese patients with chronic HCV infection, and to identify significant predictors of the HRQoL in these patients of China.

Methods: In this cross-sectional observational study, treatment-naïve Han ethnic adults with chronic HCV infection were enrolled. Adopting European Quality of Life scale (EQ-5D) and EuroQOL visual analogue scale (EQ-VAS) were used to qualify HRQoL. Results were reported in descriptive analyses to describe sociodemographic and clinical characteristics. Multiple linear regression analysis was applied to investigate the associations of these variables with HRQoL. Binary logistic regression analysis was performed to identify associations of these variables with HRQoL by dimensions of EQ-5D.

Results: Nine hundred ninety-seven patients were enrolled in the study [median age 46.0 (37.0, 56.0) years; male 54.8%]. Mean EQ-5D index and EQ-VAS score were 0.780 ± 0.083 and 77.2 ± 14.8. Multiple Linear regression analysis showed that income (< 2000 RMB, β = - 0.134; 2000-4999 RMB, β = - 0.085), moderate or severe symptoms of discomfort (more than one symptoms, β = - 0.090), disease profile (cirrhosis, β = - 0.114), hyperlipidemia (β = - 0.065) and depression (β = - 0.065) were independently associated with EQ-5D index. Residence (the west, β = 0.087), income (< 2000 RMB, β = - 0.129; 2000-4999 RMB, β = - 0.052), moderate or severe symptoms of discomfort (more than one symptoms, β = - 0.091), disease profile and depression (β = - 0.316) were the influencing factors on EQ-VAS. Binary logistic regression indicated that disease profile and clinical depression were the major influencing factors on all five dimensions of EQ-5D.

Conclusions: In this cross-sectional assessment of HCV patients in China, we indicated HRQoL of Chinese HCV patients. Significant negative associations between HRQoL and sociodemographic and clinical factors such as moderate or severe symptoms of discomfort, disease profile and depression emerged. We have to focus on optimally managing care of HCV patients and improving their HRQoL.

Trial Registration: ClinicalTrials.gov identifier NCT01293279. Date of registration: February 10, 2011.
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http://dx.doi.org/10.1186/s12955-018-0941-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003185PMC
June 2018

Risk Assessment of Hepatocellular Carcinoma in Patients with Hepatitis C in China and the USA.

Dig Dis Sci 2017 11 25;62(11):3243-3253. Epub 2017 Sep 25.

Division of Gastroenterology and Hepatology, University of Michigan Health System, 1500 E Medical Center Dr, Taubman Center SPC 3912, Ann Arbor, MI, USA.

Background: Hepatitis C (HCV) infection is an increasingly common cause of hepatocellular carcinoma (HCC) in China.

Aims: We aimed to determine differences in demographic and behavioral profiles associated with HCC in HCV+ patients in China and the USA.

Methods: Consecutive HCV+ patients were recruited from centers in China and the USA. Clinical data and lifestyle profiles were obtained through standardized questionnaires. Multivariable analysis was conducted to determine factors associated with HCC diagnosis within groups.

Results: We included 41 HCC patients from China and 71 from the USA, and 931 non-HCC patients in China and 859 in China. Chinese patients with HCC were significantly younger, less likely to be male and to be obese than US patients with HCC (all p < 0.001). Chinese patients with HCC had a significantly lower rate of cirrhosis diagnosis (36.6 vs. 78.9%, p < 0.001); however, they also had a higher rate of hepatitis B core antibody positivity (63.4 vs. 36.8%, p = 0.007). In a multivariable analysis of the entire Chinese cohort, age > 55, male sex, the presence of diabetes, and time from maximum weight were associated with HCC, while tea consumption was associated with a decreased HCC risk (OR 0.37, 95% CI 0.16-0.88). In the US cohort, age > 55, male sex, and cirrhosis were associated with HCC on multivariable analysis.

Conclusions: With the aging Chinese population and increasing rates of diabetes, there will likely be continued increase in the incidence of HCV-related HCC in China. The protective effect of tea consumption on HCC development deserves further validation.
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http://dx.doi.org/10.1007/s10620-017-4776-7DOI Listing
November 2017

Abnormal phenotypic features of IgM+B cell subsets in patients with chronic hepatitis C virus infection.

Exp Ther Med 2017 Aug 27;14(2):1846-1852. Epub 2017 Jun 27.

Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease, Peking University People's Hospital, Peking University Hepatology Institute, Beijing 100044, P.R. China.

Hepatitis C virus (HCV) infection is associated with B cell abnormality; however the phenotypic profiles of immunoglobulin (Ig)M+B cell subsets in patients with HCV infection remain unclear. In the current study, the effect of HCV infection on IgM+B cell subsets was evaluated. The percentages, as well as the differentiation and activation features of peripheral IgM+B naive subsets [cluster of differentiation (CD)27-IgM+B cells] and IgM+B memory subsets (CD27+IgM+B cells) were assessed using flow cytometry in 27 patients with chronic hepatitis C (CHC) and 20 healthy controls (HCs). The frequency of CD27+IgM+B memory subsets detected in patients with CHC was significantly higher than that in HCs (P<0.05). Although the frequency of CD27-IgM+B naive subsets was similar in both groups, there was a significantly higher proportion of CD5+B cells detected in the CD27-IgM+B subsets of patients with CHC compared with HCs (P<0.05). Among CD27-IgM+B subsets, abnormal differentiation was associated with HCV infection, with significantly increased percentages of IgD+B cells and CD38+B cells in patients with CHC compared with HCs (P<0.05). In CD27+IgM+B memory subsets, the abnormality of cell differentiation was associated with a significantly increased percentage of CD38+B cells in patients with CHC compared with HCs (P<0.05). In addition, the percentage of activated CD27+IgM+B subsets in patients with CHC were significantly higher than those observed in HCs (P<0.05). The number of CD27-IgD+IgM+B, CD27-CD38+IgM+B and CD27+CD38+IgM+B cells were negatively correlated with HCV RNA in patients with CHC. These results suggest that HCV infection contributes to abnormalities in the percentage, differentiation and activation of IgM+B cell subsets and may disrupt the immune response mediated by IgM+B cells.
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http://dx.doi.org/10.3892/etm.2017.4682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525653PMC
August 2017

Temporal Changes in the Modes of Hepatitis C Virus Transmission in the USA and Northern China.

Dig Dis Sci 2017 08 1;62(8):2141-2149. Epub 2017 Jun 1.

Division of Gastroenterology and Hepatology, University of Michigan Health System, 1500 E Medical Center Drive, 3912 Taubman Center, SPC 5362, Ann Arbor, MI, 48109, USA.

Background: Predominant modes of hepatitis C virus (HCV) transmission vary between countries and over time.

Aims: To compare HCV transmission modes in the USA and northern China.

Methods: We conducted a prospective study enrolling two cohorts of chronic HCV patients in the USA, and in China at Beijing, and at Gu'an and Kuancheng counties in Hebei. Patients self-reported the most likely source and year of infection.

Results: A total of 1957 patients were studied (1000 USA; 957 China-428 Beijing, 387 Gu'an, 142 Kuancheng). The predominant infection sources were transfusion (23.0%) and injection drug use (IDU) (32.1%) in the USA and transfusion (64.5%) in northern China. Within China, transfusion was the most common source in Beijing (62.1%) and Gu'an (88.1%), and medical procedures (35.9%) and IDU (12.0%) in Kuancheng. Infection via transfusion decreased significantly in the USA (35.1-4.6%) and Beijing (84.2-14.3%) but remained frequent in Gu'an (90.5-72.5%) over time. Infection via IDU decreased from 32.4% in those ≥61 years to 25.0% in those 41-50 years but increased to 46.5% in those ≤40 years in US patients and decreased over time from 38.7 to 1.9% in Kuancheng. Infection via medical procedures increased over time in Beijing (7.0-33.3%) and remained frequent in Kuancheng (45.2-31.1%).

Conclusions: There are major differences in presumed HCV infection source between the USA and northern China. Favorable as well as worrisome changes in the modes of HCV transmission in both countries were observed.
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http://dx.doi.org/10.1007/s10620-017-4619-6DOI Listing
August 2017

Association of ATP-Binding Cassette Transporter (ABC) Gene Polymorphisms with Viral Load in Patients with Genotype 1 Hepatitis C Virus Infection.

Clin Lab 2016 Sep;62(9):1643-1649

Background: ATP-binding cassette transporters (ABC) gene polymorphisms are associated with various biological functions, including hepatitis C virus (HCV) infection. This study aims to explore the impact of ABC transporters polymorphisms on HCV viral load in chronic treatment-naïve hepatitis C patients.

Methods: We recruited 347 Chinese Han patients chronically infected with genotype 1 HCV in this study. Ten single nucleotide polymorphism (SNPs) in ABCA1, ABCB5, ABCB11, ABCG2, ABCG5, ABCG10 were analyzed by custom chip from Illumina. Allele frequency analysis and genotype frequency analysis were performed.

Results: Patients were categorized according to pretreatment HCV viral load (VL) with a cutoff level 600 000 IU/mL. No significant variations on gender and age were observed in the two groups. G allele of rs3890182 and C allele of rs1883025 in ABCA1 gene were significantly associated with lower HCV viral load (p = 0.013 and p = 0.006) in allele frequency analysis. GG genotype of rs3890182 and CC genotype of rs1883025 in ABCA1 gene were significantly associated with lower HCV viral load (p = 0.027 and p = 0.013) in genotype frequency analysis. Quantitative analysis showed significantly lower viral load in patients with CC genotype of rs1883025 (p = 0.012). Allele associated lower HCV viral load was reported to be associated with higher HDL cholesterol level.

Conclusions: Our finding suggests that ABCA1 gene polymorphism in rs1883025 is significantly associated with HCV VL in patients infected with HCV genotype 1.
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http://dx.doi.org/10.7754/Clin.Lab.2016.160105DOI Listing
September 2016

Serum HBV core-related antigen is a good predictor for spontaneous HBeAg seroconversion in chronic hepatitis B patients.

J Med Virol 2017 03 31;89(3):463-468. Epub 2016 Aug 31.

Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.

Early prediction of spontaneous hepatitis B virus e antigen (HBeAg) seroconversion is pivotal in the prevention of unnecessary drug prescription, corresponding financial burden, and adverse reactions. One hundred and thirteen chronic hepatitis B patients with HBeAg-positive in the immune active phase were followed up for about 1.5 years. Patients were classified into two groups: spontaneous HBeAg seroconversion group (group A, n = 18) and non-spontaneous HBeAg seroconversion group. Among the non-spontaneous HBeAg seroconversion group, 35 patients were selected as controls (group B, n = 35). At week 12, there was a significant difference in hepatitis B core-related antigen (HBcrAg) levels between the two groups (group A 4.32 ± 1.05 log  kU/ml, and group B 5.16 ± 0.53 log  kU/ml, P = 0.004), and this significance magnified at week 28. Only two variables, HBcrAg level and the reduction in the HBcrAg levels (ΔHBcrAg) at week 28 were enrolled, with the odds ratio of 4.19 and 0.21, respectively. The optimal cutoffs of HBcrAg levels and the ΔHBcrAg at week 28 were 4.90 and 2.00 log  kU/ml, respectively. The positive predictive value and negative predictive value of HBcrAg levels at week 28 were 73.9% and 96.7%, respectively. The positive predictive value and negative predictive value of the ΔHBcrAg at week 28 were 76.2% and 93.8%, respectively. The measurement of HBcrAg is useful for monitoring the natural course of chronic hepatitis B virus infection. The dynamics of HBcrAg levels could accurately predict the spontaneous HBeAg seroconversion. J. Med. Virol. 89:463-468, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24657DOI Listing
March 2017

Hepatitis C Virus Genotype Analyses in Chronic Hepatitis C Patients and Individuals With Spontaneous Virus Clearance Using a Newly Developed Serotyping Assay.

J Clin Lab Anal 2017 Jan 13;31(1). Epub 2016 Jun 13.

Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, China.

Background: We developed a novel HCV serotyping assay and detected the genotypes in chronic hepatitis C (CHC) patients and individuals with spontaneous viral clearance (SVC).

Methods: Nine hundred and ninety-seven patients were enrolled in a previous study; their samples were genotyped originally using the molecular assays. Among them, 190 patients achieved sustained virological response; the post-treatment samples were also serotyped. Moreover, 326 samples from follow-up cohorts were serotyped, among whom 66 were from SVC individuals, and 260 from CHC patients.

Results: Nine hundred and fifty-eight out of 997 samples were available for serotyping, among which 29 samples generated indeterminate serotyping results. The consistency between the genotyping and serotyping assays was 91.50% (850/929). The specificity and sensitivity were 98.45% and 88.77% for genotype 1, 96.42% and 93.97% for genotype 2, and 94.15% and 80.52% for non-genotype 1 or 2. However, only 41 of 60 genotype-6 samples were correctly serotyped. Little difference was found in the 190 paired serotyping results. No difference existed in the genotype distribution between the SVC and CHC groups (P = 0.08).

Conclusions: The assay provides an accurate alternative for determining HCV genotypes, whereas it is not recommended for detecting genotype 6. Furthermore, it facilitates identifying the genotypes in SVC individuals. HCV genotype has little impact on SVC.
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http://dx.doi.org/10.1002/jcla.22014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817036PMC
January 2017
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