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Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma

World Journal of Gastroenterology 2022年第29期28卷 3917-3933页

作者： Juliane Malik Martin Klammer Vinzent Rolny henry lik-yuen chan Teerha Piratvisuth Tawesak Tanwandee Satawat Thongsawat Wattana Sukeepaisarnjaroen Juan Ignacio Esteban Marta Bes Bruno Kohler Magdalena Swiatek-de Lange Diagnostics GmbH Penzberg 82377Germany Faculty of Medicine The Chinese University of Hong KongHong Kong 999077China NKC Institute of Gastroenterology and Hepatology Songklanagarind HospitalHat Yai 90112Thailand Division of Gastroenterology Faculty of MedicineSiriraj HospitalMahidol UniversityBangkok 10700Thailand Department of Internal Medicine Maharaj Nakorn Chiang Mai HospitalChiang Mai UniversityChiang Mai 50200Thailand Faculty of Medicine Srinagarind HospitalKhon Kaen UniversityKhon Kaen 40000Thailand Liver Unit Vall d’Hebron University HospitalBarcelona 08035Spain Transfusion Safety Laboratory Banc de Sang i TeixitsBarcelona 08005Spain Department of Medical Oncology National Center for Tumor DiseasesUniversity Hospital HeidelbergHeidelberg 69120Germany Liver Cancer Center Heidelberg University Hospital HeidelbergHeidelberg 69120Germany

BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein(AFP), protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs(miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including *** To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein *** Our prospective, multicenter, case-control study recruited 660 participants(354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR(n = 60) and next-generation sequencing(n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs(including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-Ⅱ via real-time quantitative PCR in training(n = 200) and validation cohorts(n = 300).RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from(early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p(miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423could significantly distinguish(Q < 0.05) between the HCC and chronic liver disease control grou

关键词： Carcinoma Hepatocellular MicroRNAs Biomarkers Alpha-fetoprotein Protein induced by vitamin K absence-Ⅱ Diagnosis

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Stopping nucleos(t)ide analog treatment in chronic hepatitis B-Who and when?

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Liver Research 2017年第2期1卷 135-139页

作者： Suzette Grace R.Kho-Herman henry lik-yuen chan Institute of Digestive Disease The Chinese University of Hong KongHong KongChina Makati Medical Center MakatiPhilippines

Nucleos(t)ide analogs(NAs)are one of the first-line treatments for chronic hepatitis B(CHB)*** are highly efficient in suppressing viral replication but are associated with a low rate of hepatitis B surface antigen(HBsAg)seroclearance and a high risk of post-treatment virologic *** a result,the optimal timing of NA cessation remains unclear,and long-term treatment is often *** international guidelines suggest that NA can be discontinued in hepatitis B e antigen(HBeAg)-positive patients who achieve HBeAg seroconversion with undetectable hepatitis B virus(HBV)DNA levels,the recommendations for discontinuing NA treatment in HBeAg-negative patients remain ***,there is no consensus regarding in whom and when to restart treatment among patients with hepatitis relapse after stopping NA *** studies suggest that virologic markers such as HBsAg and hepatitis B core-related antigen(HBcrAg)titers may be useful to guide when to stop NAs in CHB,since both markers appear to correlate with intrahepatic covalently closed circular HBV DNA ***,additional studies are required to refine their use.

关键词： Hepatitis B Entecavir Tenofovir Hepatitis B virus deoxyribonucleic acid (HBV DNA) Hepatitis B surface antigen(HBsAg) Hepatitis B core-related antigen(HBcrAg) Hepatitis B e antigen(HBeAg)

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Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis

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World Journal of Gastroenterology 2019年第32期25卷 4715-4726页

作者： Ran-Xu Zhu Alfred Sze Lok Cheng henry lik yuen chan Dong-Ye Yang Wai-Kay Seto Department of Gastroenterology and Hepatology The University of Hong Kong–Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell ***2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor ***,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully *** To investigate the function and mechanism of GAS2 in *** GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western *** proliferation was analyzed by counting,MTS,and colony formation *** cycle analysis was performed by flow *** apoptosis was investigated by Annexin V apoptosis assay and western *** GAS2 protein expression was lower in HCC than in normal *** of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(Pchanges of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(P<0.05).CONCLUSION GAS2 plays a vital role in HCC cell proliferation and apoptosis,possibly by regulating the cell cycle and p53-dependent apoptosis pathway.

关键词： Growth arrest-specific gene 2 Cell cycle Apoptosis Hepatocellular carcinoma p53-dependent signaling pathway

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乙型肝炎抗病毒治疗2014年国内外进展

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中华肝脏病杂志 2015年第1期23卷 2-4页

作者：张伟贾继东陈力元首都医科大学附属北京友谊医院肝病中心 100050 香港中文大学威尔斯亲王医院胃肠及肝病科

目前全球已批准用于治疗慢性乙型肝炎（CHB）的药物仍然仅包括干扰素类（IFN）如普通干扰素和聚乙二醇干扰素（Peg-IFN）,及核苷（酸）类似物（NA）如拉米夫定（LAM）、阿德福韦（ADV）、恩替卡韦（ETV）、替比夫定（LdT）、替诺福韦酯... 详细信息

目前全球已批准用于治疗慢性乙型肝炎（CHB）的药物仍然仅包括干扰素类（IFN）如普通干扰素和聚乙二醇干扰素（Peg-IFN）,及核苷（酸）类似物（NA）如拉米夫定（LAM）、阿德福韦（ADV）、恩替卡韦（ETV）、替比夫定（LdT）、替诺福韦酯（TDF）等.前一类药物可使部分患者实现HBeAg血清学转换,后一类药物可在大部分患者实现有效抑制HBV复制,从而阻断或延缓疾病进展.

关键词：肝炎病毒,乙型治疗进展

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慢性乙型肝炎与代谢综合征的关系

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中华肝脏病杂志 2009年第11期17卷 807-808页

作者：陈力元施军平香港中文大学威尔斯亲王医院内科及药物治疗学系浙江中医药大学附属杭州第六医院肝病科

在亚洲，慢性乙型肝炎（CHB）是导致肝硬化和肝细胞癌的最常见原因，目前已证实可促进肝纤维化和肝硬化发生的危险因素包括：年龄大，男性，饮酒，合并感染丙型肝炎病毒（HCV）、丁型肝炎病毒和人类免疫缺陷病毒，ALT升高，高HBV DNA载... 详细信息

在亚洲，慢性乙型肝炎（CHB）是导致肝硬化和肝细胞癌的最常见原因，目前已证实可促进肝纤维化和肝硬化发生的危险因素包括：年龄大，男性，饮酒，合并感染丙型肝炎病毒（HCV）、丁型肝炎病毒和人类免疫缺陷病毒，ALT升高，高HBV DNA载量，基因C型等。Iloeje等一项随访超过10年的前瞻性研究显示肝硬化发生与HBV DNA载量相关。

关键词：肝炎病毒,乙型脂肪肝肝纤维化肝硬化超声检查

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Clinical significance of hepatic derangement in severe acute respiratory syndrome

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World Journal of Gastroenterology 2005年第14期11卷 2148-2153页

作者： henry lik-yuen chan Ambrose Chi-Pong Kwan Ka-Fai To Sik-To Lai Paul Kay-Sheung chan Wai-Keung Leung Nelson Lee Alan Wu Joseph Jao-Yiu Sung Department of Medicine and Therapeutics Chinese University of Hong Kong Hong Kong SARChina Department of Medicine Princess Margaret Hospital Hong Kong SARChina Department of Anatomical and Cellular Pathology Chinese University of Hong Kong Hong Kong SARChina Department of Microbiology Chinese University of Hong Kong Hong Kong SARChina

AIM: Elevation of alanine aminotransferase (ALT) level is commonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS ***: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and ***: Two hundred and ninety-four patients were included in this study. Seventy (24%) patients had elevated serum ALT on admission and 204 (69%) patients had elevated ALT during the subsequent course of illness. Using peak ALT >5×ULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peak ALT>5x ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95% CI 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34(95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical ***: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severe hepatitis had worse clinical outcome.

关键词：肝功能紊乱严重急性呼吸综合症丙胺酸转氨酶并发症

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Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment

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World Journal of Gastroenterology 2003年第12期9卷 2695-2697页

作者： henry lik-yuen chan May-Ling Wong Alex Yui Hui Angel Mei-Ling Chim Ada Mei-Ling Tse Lawrence Cheung-Tsui Hung Francis Ka-Leung chan Joseph Jao-Yiu Sung Department of Medicine and Therapeutics Chinese University of Hong KongHong Kong

AIM: To investigate the association of hepatitis B virus (HBV) genotype and HBeAg seroconversion after nucleotide analogue ***: Chronic hepatitis B patients receiving lamivudine followed up for at least 6 months post-treatment were studied. Consecutive treatment-naive patients who were prospectively followed up in the clinic for at least 18 months were studied as controls. HBeAg seroconversion was defined as loss of HBeAg, appearance of anti-HBe and normalization of alanine aminotransferase for at least 6 ***: Thirty-five patients on lamivudine and 96 control patients followed up for 39 (18-49) months were *** was given for 12 (10-18) months, and patients were followed up for 15 (6-34) months after drug *** B and C HBV were found in 43 and 88 patients and HBeAg seroconversion occurred in 12 (28 %) and 16(18 %) patients, respectively (P=0.30). There was no difference in HBeAg seroconversion between patients infected by genotype B and C HBV in the control (35 % vs 21%, P=0.25) and lamivudine-treated (14 % vs 10 %,P=1.00) ***: HBeAg seroconversion after treatment by lamivudine was not influenced by the HBV genotype.

关键词：乙型肝炎乙型肝炎病毒拉米夫定 HBeAg 基因型抗病毒治疗

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非酒精性脂肪性肝病的治疗

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中华肝脏病杂志 2007年第9期15卷 687-688页

作者：黄炜燊范建高陈力元香港中文大学消化疾病研究所和内科学药物治疗部上海交通大学附属第一人民医院脂肪肝诊治中心

非酒精性脂肪性肝病（NAFLD）及其主要类型一非酒精性脂防性肝炎（NASH）,不仅是肝酶持续异常的首要病因,而且可导致失代偿期肝硬化、肝细胞癌以及肝衰竭。随着亚洲地区肥胖症和糖尿病患者的不断增多,近期NAFLD或NASH的患病率仍将不断... 详细信息

非酒精性脂肪性肝病（NAFLD）及其主要类型一非酒精性脂防性肝炎（NASH）,不仅是肝酶持续异常的首要病因,而且可导致失代偿期肝硬化、肝细胞癌以及肝衰竭。随着亚洲地区肥胖症和糖尿病患者的不断增多,近期NAFLD或NASH的患病率仍将不断攀升并呈现出低年龄化的发病趋势。为此,亚太地区NAFLD工作组起草了NAFLD诊疗指南,无疑这将对本地区NAFLD的诊断和治疗起到重要指导作用。

关键词：脂肪肝治疗学

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慢性乙型肝炎患者144周治疗期间未发现丙酚替诺福韦耐药

慢性乙型肝炎患者144周治疗期间未发现丙酚替诺福韦耐药

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第十届全国疑难及重症肝病大会

作者： henry lik-yuen chan Patrick Marcellin Calvin Q.Pan Andrea L Cathcart Neeru Bhardwaj Yang Liu Bandta Parhy Eric Zhou David Hsieh Silvia chang Ross Martin Becket Feierbach Hongmei Mo Anuj Gaggar John F Flaherty Shalimar Namiki Izumi Young-Suk Lim The Chinese University of Hong Kong

背景在2项评价丙酚替诺福韦(TAF)或富马酸替诺福韦二吡呋酯(TDF)用于HBeAg+或HBeAg-慢性乙型肝炎初治或经治成人患者时的3期临床研究(GS-US-320-0108,GS-US-320-0110)中进行了累积耐药性分析。方法患者按照2:1的比例进行随机分组,并按照...

背景在2项评价丙酚替诺福韦(TAF)或富马酸替诺福韦二吡呋酯(TDF)用于HBeAg+或HBeAg-慢性乙型肝炎初治或经治成人患者时的3期临床研究(GS-US-320-0108,GS-US-320-0110)中进行了累积耐药性分析。方法患者按照2:1的比例进行随机分组,并按照HBV DNA水平和治疗状态进行分层接受TAF

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丙酚替诺福韦(TAF)和富马酸替诺福韦二吡呋酯(TDF)治疗用于HBeAg阴性和HBeAg阳性的慢性乙型肝炎患者三年疗效和安全性对比

丙酚替诺福韦(TAF)和富马酸替诺福韦二吡呋酯(TDF)治疗用于HBeAg...

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第十届全国疑难及重症肝病大会

作者： henry lik yuen chan Young-Suk LIM Wai Kay Walter Seto Kosh Agarwal Maurizia R.Brunetto Harry L.A.Janssen Florin Caruntu Tatjana Stepanova Owen Tsang Hiroshi Yatsuhashi Won Young Tak Chi-Yi Chen Mustafa Celen Vithika Suri John F.Flaherty Lanjia Lin Andrea Cathcart Anuj Gaggar Cong Cheng Calvin Q.Pan Shalimar Maria Buti Institute of Digestive Disease Department of Medicine and Therapeuticsand State Key Laboratory of Digestive DiseaseThe Chinese University of Hong Kong Gastroenterology Asan Medical CenterUniversity of Ulsan College of Medicine Queen Mary Hospital Institute of Liver Studies King’s College Hospital NHS Trust Hepatology Unit University Hospital of Pisa Toronto Centre for Liver Disease University Health Network Infectious Diseases National Institute for Infectious Diseases Matei Bals Modern Medicine Clinic Princess Margaret Hospital National Hospital Organization Nagasaki Medical Center Kyungpook National University Hospital Chia-Yi Christian Hospital Gilead Sciences Inc NYU Langone Medical Center Gastroenterology All India Institute of Medical Sciences Hospital Universitari Vall d’Hebron Dicle University Hospital Infectious Diseases

背景在2项设计相同的双盲、随机(2:1)、3期研究中,第48周和第96周时,TAF的疗效不劣于TDF,而且具有良好的肾脏和骨骼安全性。方案修订后,50%的入组患者的双盲(DB)治疗期再延长1年,而其余受试者在第96周(第2年)时更换为开放标签(OL)TAF。...

背景在2项设计相同的双盲、随机(2:1)、3期研究中,第48周和第96周时,TAF的疗效不劣于TDF,而且具有良好的肾脏和骨骼安全性。方案修订后,50%的入组患者的双盲(DB)治疗期再延长1年,而其余受试者在第96周(第2年)时更换为开放标签(OL)TAF。本研究评估了3年TAF和TDF治疗在接受相应药物的患者中的安全性和疗效对比结果。

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