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Direct acting antiviral-induced dynamic reduction of serum a fetoprotein in hepatitis C patients without hepatocellular carcinoma

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Frontiers of Medicine 2019年第6期13卷 658-666页

作者： Tung huynh ke-qin hu Department of Pharmacy University of CaliforniaIrvineSchool of MedicineOrangeCA 92868USA Division of Gastroenterology and Hepatology University of CaliforniaIrvineSchool of MedicineOrangeCA 92868USA

Direct acting antiviral(DAA)treatments may reduce the elevatedαfetoprotein(AFP),but data on how these treatments affect elevated AFP in patients with chronic hepatitis C(CHC)remain *** the present study,the frequency of baseline AFP elevations and their related factors,AFP dynamics during and after DAA treatment,and factors associated with AFP reduction was *** retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological *** details are as follows:mean post-treatment follow-up was 99 weeks(12–213);mean age,57.8 years old;52%,males;79%,genotype(GT)1;and 47%,***-treatment AFP elevation(>5.5 ng/mL)was seen in 48.2%*** multivariate analysis,baseline AFP>5.5 was associated with the presence of cirrhosis(P=0.001),co-existing non-alcoholic steatohepatitis(NASH)(P=0.035),and GT 1(P=0.029).AFP normalization was seen in 28.2%patients at treatment week 2,in 52%at the end of treatment,and in 73.4%at the end of ***-treatment week 24 AFP normalization was associated with the absence of cirrhosis(P=0.003),Child--Pugh score<6(P=0.015),and baseline AFP<10(P=0.015).AFP elevation is common in patients with CHC and independently associated with NASH,cirrhosis,and GT *** treatment resulted in AFP normalization as early as treatment week ***-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis,Child--Pugh score<6,and baseline AFP<10.

关键词： chronic hepatitis C αfetoprotein direct acting antiviral treatment cirrhosis

Advances in some common chronic liver diseases

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Frontiers of Medicine 2014年第2期8卷 127-128页

作者： ke-qin hu Division of Gastroenterology and Hepatology University of California Irvine School of Medicine Orange CA 92868 USA

Chronic liver diseases （CLDs） are a diversified group of primary hepatic pathophysiological injury caused by various infectious, genetic and metabolic, hepatotoxic, autoimmune, and other underlying etiologies. If diagnosis and treatment are delayed, most CLDs could progress to cirrhosis that can be further associated with development of hepatocellular carcinoma （HCC）. Significant medical advances have been made in diagnosing and treating CLDs. We are very pleased to present this special issue of Frontiers of Medicine that covers some important topics in clinical hepatology.

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Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts in nude mice

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World Journal of Gastroenterology 2009年第16期15卷 1943-1950页

作者： Wei Cui Fan Gu ke-qin hu Division of Gastroenterology and Chao Family Comprehensive Cancer Center University of California Orange School of Medicine Orange CA 92868 United States Department of Surgery Nanfang Hospital Southern Medical University Guangzhou 510515 Guangdong Province China

AIM:To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude ***: Nude mice bearing huH7 xenografts were used to assess the anti-HCC effects and mechanisms of ***: Silibinin resulted in a potent dosedependent reduction of huH7 xenografts in association with a significant decrease in Ki-67 and α-fetoprotein production, nuclear NF-κB content, polo-like kinase 1, Rb phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced apoptosis of huH7 xenografts was associated with inhibited survivin phosphorylation. Silibinin-reduced growth of huH7 xenografts was associated with decreased p-ERK, increased PTEN expression and the activity of silibinin was correlated with decreased p-Akt production, indicating involvement of PTEN/PI3K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin-reduced growth of huH7 xenografts was also associated with a significant increase in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-***: Silibinin reduces HCC xenograft growth through the inhibition of cell proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing cell apoptosis, and increasing histone acetylation and SOD-1 expression.

关键词： Apoptosis Cell cycle Chemoprevention Hepatocellular carcinoma Histone acetylation Silibinin

New perspective on the natural course of chronic HBV infection

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Frontiers of Medicine 2014年第2期8卷 129-134页

作者： Yong-Yuan Zhang ke-qin hu Zhongping Duan HB Vtech LLC 13901 Lullaby RD Germantown MD 20874 USA Division of Gastroenterology and Hepatology University of California Irvine School of Medicine Orange CA 92868 USA You An Hospital Capital Medical University Beijing 100069 China

Chronic hepatitis B virus （HBV） infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen （HBeAg） seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

关键词： hepatitis B virus chronic HBV infection natural course hepatitis B seroconversion

Hepatitis C Virus Clearance by Direct-acting Antiviral Results in Rapid Resolution of Hepatocytic Injury as Indicated by Both Alanine Aminotransferase and Aspartate Aminotransferase Normalization

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Journal of Clinical and Translational Hepatology 2018年第3期6卷 258-263页

作者： Tung huynh Johnathan Zhang ke-qin hu Division of Gastroenterology and Hepatology School of MedicineUniversity of CaliforniaOrangeCAUSA

Background and Aims:Hepatitis C virus(HCV)infection results in hepatocytic injury with elevation of both alanine aminotransferase(ALT)and aspartate aminotransferase(AST).It remains to be determined if direct-acting antiviral treatment can terminate hepatocytic injury following viro-logic *** this end,we evaluated the pattern and predicting factors of ALT and AST normalization during and after direct-acting antiviral treatment with sustained virologic response at 12 weeks(SVR12).Methods:Single-center ret-rospective study on 115 HCV-infected patients who achieved SVR12 was ***:At treatment week 2,100%and 45.9%showed decline in HCV RNA to<700 IU/mL and undetectable levels,respectively,and this was associated with 85.5%,83.9%and 77.4%ALT normalization,AST nor-malization and ALT and AST *** end of treat-ment,85.6%of patients with baseline elevation of both ALT and AST had normalization of both ALT and *** posttreat-ment weeks 12 and 24,90.8%and 94.8%had normalization of both ALT and *** clearance also resulted in further decline of both ALT and AST in those with baseline<40 *** analysis showed baseline Child-Pugh score of<6,model for end-stage liver disease score of<10,HCV geno-type 1,and HCV RNA of<500 IU/mL at treatment week 2 were associated with sustained normalization of both ALTand AST at posttreatment week *** multivariate analysis,baseline model for end-stage liver disease score of<10 was significantly associated with normalization of both ALT and AST at posttreatment week 12,independent of baseline Child-Pugh score<6,HCV genotype 1,and HCV RNA of<500 IU/mL at treatment week ***:During direct-acting antiviral therapy,85.5%and 83.9%had nor-malization of both ALTand ASTas early as in week 2,providing;biochemical evidence of hepatocytic injury *** normalization of both ALT and AST was seen in 90.8%at posttreatment weeks 12,and was independently associated with baseline model for end-sta

关键词： Chronic hepatitis C Direct acting antiviral ALTand AST normalization Hepatocytic injury

Overview on acute-on-chronic liver failure

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Frontiers of Medicine 2016年第1期10卷 1-17页

作者： Jing Zhang Shan Gao Zhongping Duan ke-qin hu Department of Hepatitis C and Drug Induced Liver Injury Beijing YouAn Hospital Capital Medical University Beij'ing 100069 China Beijing Artificial Liver Treatment & Training Center Beijing YouAn Hospital Capital Medical University~ Be~'ng 100069 Chinai' Collaborative Innovation Center of lnfectious Diseases Beijing 100069 China Division of Gastroenterology and Hepatology University of California Irvine Medical Center Orange CA 92868 USA

Liver failure （LF） is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. CHnical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF （ACLF）, and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.

关键词： liver failure chronic liver failure acute-on-chronic liver failure diagnosis prognosis treatment

Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

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World Journal of Hepatology 2024年第7期16卷 1009-1017页

作者： Tung huynh Delana MyAn Bui Tina Xiwen Zhou ke-qin hu Department of Pharmacy University of California Irvine Medical CenterOrangeCA 92868United States University of Houston HoustonTX 77204United States Chicago Medical School at Rosalind Franklin University North ChicagoIL 60064United States Division of Gastroenterology and Hepatology University of California IrvineSchool of MedicineOrangeCA 92868United States

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic *** To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with *** A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated *** The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,*** 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,*** baseline to switching week 144,the rates of ALT and AST60 mL/min was increased from 86.5%at baseline to 88.2%at switching week *** Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

关键词： Tenofovir alafenamide Tenofovir disoproxil fumarate Switching Hepatic fibrosis improvement Aspartate aminotransferase to platelet ratio index Fibrosis-4 Shear wave elastography

Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals

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World Journal of Hepatology 2019年第5期11卷 442-449页

作者： ke-qin hu Wei Cui Susan D Rouster kenneth E Sherman Division of GI/Hepatology University of CaliforniaIrvineSchool of MedicineOrangeCA 92868United States Division of Digestive Diseases University of Cincinnati College of MedicineCincinnatiOH 45267United States

BACKGROUND Current diagnosis of hepatitis C virus(HCV)infection requires two sequential steps:testing for anti-HCV followed by HCV RNA PCR to confirm *** have developed a highly sensitive and specific HCV-antigens enzyme immunoassay(HCV-Ags EIA)for one-step diagnosis of viremic HCV *** To assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus(HIV)-coinfected *** The study blindly tested HCV-Ags EIA for its performance in one-step diagnosing viremic HCV infection in 147 sera:10 without HCV or HIV infection;54 with viremic HCV monoinfection;38 with viremic HCV/HIV coinfection;and 45 with viremic HCV and non-viremic HIV *** Upon decoding,it was 100%accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR *** five sera with HCV infection,HCV RNA was as low as 50-59 IU/mL,and four out of five tested positive for HCV-Ags ***,it was also 100%accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR in 83 sera with HCV and HIV coinfection,regardless if HIV infection was active or *** The modified HCV-Ags EIA has a lower detection limit equivalent to serum HCV RNA levels of approximately 100 IU/*** is highly sensitive and specific in the setting of HIV coinfection,regardless of HIV infection status and CD4 *** data support the clinical application of the HCV-Ags EIA in one-step diagnosis of HCV infection in HIV-infected individuals.

关键词： Hepatitis C virus Hepatitis C virus antigens Hepatitis C virus core antigen Hepatitis C virus diagnostic test Diagnostic assay Enzyme immunoassay

New Year’s greeting and overview of World Journal of Hepatology in 2021

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World Journal of Hepatology 2021年第1期13卷 1-5页

作者： ke-qin hu Koo Jeong Kang Nikolaos Pyrsopoulos Xiang Li Division of Gastroenterology and Hepatology University of CaliforniaIrvine Medical CenterOrangeCA 92868United States Division of Hepatobiliary Pancreatic Surgery Department of SurgeryKeimyung University Dong-San Medical CenterDaegu 41931South Korea Medicine-Gastroenterology and Hepatology Rutgers-New Jersey Medical SchoolNewarkNJ 07103United States Production Department Baishideng Publishing Group IncPleasantonCA 94566United States

The World Journal of Hepatology(WJH)was launched in October *** mainly publishes articles reporting research findings in the field of hepatology,covering a wide range of topics,including viral hepatitis B and C,non-alcoholic fatty liver disease,alcoholic liver disease,autoimmune and chronic cholestatic liver disease,drug-induced liver injury,cirrhosis,liver failure,hepatocellular carcinoma,coronavirus disease 2019-related liver conditions,*** of December 31,2020,the WJH has published 1349 articles,among which,the total cites is 18995 and the average cites per article is *** celebrating the New Year,we are pleased to share with you special a New Year’s greeting from the WJH Editors-in-Chief,along with a detailed overview of the journal’s submission,peer review and publishing metrics from *** all,we are appreciative for the substantive support and submissions from authors worldwide,and the dedicated efforts and expertise provided by our invited reviewers and editorial board members.

关键词： World Journal of Hepatology New Year’s greeting message Editors-in-Chief Editorial Board Highly influential scientists Baishideng Publishing Group Inc