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World Journal of Gastroenterology 2007年第30期13卷 4085-4090页

作者： Hee Bok Chae hie-won hann Liver Disease Prevention Center Division of Gastroenterology and Hepatology Department of Medicine Jefferson Medical College and Thomas Jefferson University Hospital Philadelphia PA 19107 United States Department of Internal Medicine College of Medicine and Medical Institute Chungbuk National University Cheongju 362-711 South Korea

AIM: To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). METHODS: Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. RESULTS: The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-postitive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. CONCLUSION: Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.

关键词： Hepatitis B Lamivudine Virologic breakthrough HBV DNA

Then and now: The progress in hepatitis B treatment over the past 20 years

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World Journal of Gastroenterology 2014年第2期20卷 401-413页

作者： Dina Halegoua-De Marzio hie-won hann Division of Gastroenterology and Hepatology Department of MedicineThomas Jefferson University HospitalPhiladelphiaPA 19107United States Liver Disease Prevention Center Division of Gastroenterology and HepatologyThomas Jefferson University HospitalPhiladelphiaPA 19107United States

The ultimate goals of treating chronic hepatitis B(CHB)is prevention of hepatocellular carcinoma(HCC)and hepatic *** the advent of effective antiviral drugs that appeared during the past two decades,considerable advances have been made not only in controlling hepatitis B virus(HBV)infection,but also in preventing and reducing the incidence of liver cirrhosis and ***,several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed ***,six medications are available for HBV treatment including,interferon and five nucleoside/nucleotide *** this review,we will examine the antiviral drugs and the progresses that have been made with antiviral treatments in the field of CHB.

关键词： Chronic hepatitis B Treatment of hepatitis B Hepatocellular carcinoma Nucleoside analogues Nucleotide analogues

Long-term survival of occult hepatitis B associated hepatocellular carcinoma following surgery and antiviral therapy

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Hepatoma Research 2020年第8期6卷 29-35页

作者： Tina Boortalary Ernest Rosato Christopher Roth Xiangdong David Ren Selena YLin hie-won hann Department of Medicine Thomas Jefferson University HospitalPhiladelphiaPA 19107USA Department of Surgery Thomas Jefferson University HospitalPhiladelphiaPA 19107USA Department of Radiology Thomas Jefferson University HospitalPhiladelphiaPA 19107USA Reniguard Life Sciences Inc. MalvernPA 19355USA JBS Science Inc.DoylestownPA 18902USA Division of Liver Disease Prevention Center Division of Gastroenterology and HepatologyThomas Jefferson University HospitalPhiladelphiaPA 19107USA.

Occult hepatitis B infection(OBI)is characterized by absent hepatitis B surface antigen(HBsAg),low or undetectable serum hepatitis B viral DNA(HBV-DNA),and detectable DNA in the *** is debate over whether OBI increases the risk of hepatocellular carcinoma(HCC).We present a patient with negative HBsAg and a large HCC tumor who underwent a large right hepatic ***,the etiology of HCC was unknown,but through more sensitive molecular testing,it was believed to be due to *** this case report,we discuss the patient’s clinical course,the effect of antiviral therapy,mechanism of carcinogenesis in OBI,and the need for more rigorous HBV DNA assay testing for the detection of OBI.

关键词： Occult hepatitis B infection OBI-associated HCC HBsAg negative HCC

Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma

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Hepatoma Research 2017年第6期3卷 105-111页

作者： hie-won hann Surbhi Jain Grace Park Jamin DSteffen Wei Song Ying-Hsiu Su Liver Disease Prevention Center Division of Gastroenterology and HepatologyThomas Jefferson University HospitalPhiladelphiaPA19107USA JBS Science Inc.DoylestownPA18902USA The Baruch S.Blumberg Institute DoylestownPA18902USA.

Aim: This study aimed to explore the potential of detecting hepatocellular carcinoma (HCC)-associated DNA markers, TP53249T mutations and aberrant methylation of RASSF1A and GSTP1 genes, for monitoring HCC recurrence. HCC remains a leading cause of death worldwide, with one of the fastest growing incidence rates in the US. While treatment options are available and new ones emerging, there remains a poor prognosis of this disease mostly due to its late diagnosis and high recurrence rate. Although there are no specific guidelines addressing how HCC recurrence should be monitored, recurrence is usually monitored by serum-alpha fetal protein and imaging methods such as magnetic resonance imaging (MRI). However, early detection of recurrent HCC remains limited, particularly at the site of treated lesion. Methods: Here, the authors followed 10 patients that were treated for a primary HCC, and monitored for months or years later. At these follow-up visits, urine was collected and tested retrospectively for 3 DNA biomarkers that associate with HCC development. Results:This 10-patient study compared detection of urine DNA markers with MRI for monitoring HCC recurrence. Five patients were confirmed by MRI for recurrence, and all 5 had detectable DNA biomarkers up to 9 months before recurrence confirmation by MRI. Conclusion:Overall, this suggests that detection of HCC-associated DNA markers in urine could provide a promising tool to complement detection of recurrent HCC by imaging.

关键词： Hepatocellular carcinoma recurrence circulating-tumor DNA liver cancer biomarker urine tumor marker hepatitis B virus

血清铁蛋白:一种预后性指示剂的生物学特性及儿童成神经细胞瘤治疗中的指征

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国外医学情报 1985年第16期 273-274页

作者： hie won Lee hann 林漓美国费城Fox Chase肿瘤中心肿瘤研究所研究医师。

成神经细胞瘤患者血清中的铁蛋白含量和预后成神经细胞瘤是起源于交感神经系统的恶性肿瘤,是儿童中较常见的肿瘤之一,约占肿瘤发病率的7—10％。近年来在治疗儿童肿瘤方面尽管取得了很大的进展,但对成神经细胞瘤的疗效依然不理想。患Wil... 详细信息

成神经细胞瘤患者血清中的铁蛋白含量和预后成神经细胞瘤是起源于交感神经系统的恶性肿瘤,是儿童中较常见的肿瘤之一,约占肿瘤发病率的7—10％。近年来在治疗儿童肿瘤方面尽管取得了很大的进展,但对成神经细胞瘤的疗效依然不理想。患Wilm氏肿瘤、急性淋巴性白血病、何杰金氏病、网织细胞瘤和其它肿瘤病儿的三年存活率已达60—90％,但成神经细胞瘤病人的存活率仍在20—25％,在过去几十年中几乎没有改变。在成神经细胞瘤患儿中,有二个亚类:一类存活期较长,另一类存活期较短。前一类占成神经细胞瘤总病例数的34％,其中包括局限性肿瘤(Ⅰ期和Ⅱ期)病人,及特殊类型的

关键词：成神经细胞瘤细胞血清铁蛋白异铁蛋白儿童预后

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure

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World Journal of Hepatology 2019年第1期11卷 65-73页

作者： Brianna J Shinn Aaron Martin Robert M Coben Mitchell I Conn Jorge Prieto Howard Kroop Anthony J DiMarino hie-won hann Division of Gastroenterology and Hepatology Department of Medicine Thomas Jefferson University Hospital

Hepatitis B virus(HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma(HCC). During the last two decades, with the use of currently available anti-HBV therapies(lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBVassociated HCC(HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA(cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure(loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

关键词： Hepatitis B Hepatocellular carcinoma Antiviral therapy Persistent Risk for hepatocellular carcinoma Tumor ablation

Three primary malignancies in 17 years in a man with chronic hepatitis B

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Hepatoma Research 2019年第6期5卷 25-32页

作者： Peter D.Block Brianna J.Shinn Christopher G.Roth Jeffrey P.Baliff Ralph G.Zinner hie-wonhann Department of Medicine Thomas Jefferson University HospitalPhiladelphiaPA 19107USA Department of Radiology Abdominal Imaging DivisionThomas Jefferson University HospitalPhiladelphiaPA 19107USA Department of Pathology Anatomy&Cell BiologyThomas Jefferson University HospitalPhiladelphiaPA 19107USA Department of Medical Oncology Thomas Jefferson University HospitalPhiladelphiaPA 19107USA Liver Disease prevention Center Division of Gastroenterology and Hepatology Thomas Jefferson University HospitalPhiladelphiaPA 19107USA

The occurrence of three primary malignancies in a single patient is an infrequent phenomonen with an estimated occurrence at 0.1%.Notably,patients with hepatocellular carcinoma(HCC)are particularly unlikely to develop extrahepatic primary *** this light,we present a case of patient with chronic hepatitis B who developed HCC,as well as two other primary *** case exhibits an exceedingly rare combination of cancers,underlining the importance of continued cancer surveillence in those with a history of primary malignancy.

关键词： Hepatitis B virus hepatocellular carcinoma antiviral therapy lung cancer multiple malignancy

Erratum:Long-term survival of occult hepatitis B associated hepatocellular carcinoma following surgery and antiviral therapy

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Hepatoma Research 2022年第1期8卷 380-380页

This is an Erratum of the publsihed paper:Long-term survival of occult hepatitis B associated hepatocellular carcinoma following surgery and antiviral *** ethical approval and consent to participation information were... 详细信息

关键词： surgery hepatocellular hepatitis

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深沪湾末次冰期以来的地层结构及古环境演变

应用海洋学学报 2024年第1期43卷 126-134页

作者：王恒波李海东张汉女钟贵才许江自然资源部第三海洋研究所福建厦门361005

通过深沪湾高分辨率浅地层剖面声学地层和地质钻孔沉积地层的对比,并结合沉积物的粒度、微体古生物以及AMS14C测年的综合分析,揭示了研究区晚更新世末次冰期以来的地层层序,探讨了深沪湾的古环境演变。深沪湾高分辨率浅地层剖面自上而... 详细信息

通过深沪湾高分辨率浅地层剖面声学地层和地质钻孔沉积地层的对比,并结合沉积物的粒度、微体古生物以及AMS14C测年的综合分析,揭示了研究区晚更新世末次冰期以来的地层层序,探讨了深沪湾的古环境演变。深沪湾高分辨率浅地层剖面自上而下划分的5个声学地层单元与钻孔岩芯划分的5个沉积地层单元具有较好的对应关系。8.2 ka BP左右,全新世海侵使得海水进入深沪湾海域,海平面低于现今海平面10~12 m,气候凉爽;7 ka BP左右海水到达现今海平面位置,并于6 ka BP左右到达最高,约比现今海平面高2~3 m,气候温暖湿润,这一时期,近岸大量裸子植物被海水淹没并被沉积物快速掩埋;5 850~5 642 a BP研究区温度降低,该降温活动持续到2 ka BP左右,气候凉爽干燥;2 ka BP以来温度逐渐上升,600 a BP左右有一个相对冷期,之后温度又逐渐上升至现今水平。

关键词：海洋地质学浅地层剖面沉积层序末次冰期古环境深沪湾

Peri-Gondwanan terranes in the Romanian Carpathians:A review of their spatial distribution,origin,provenance,and evolution

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Geoscience Frontiers 2014年第3期5卷 395-411页

作者： Ioan Balintoni Constantin Balica Mihai N.Ducea Horst-Peter hann Department of Geology Babes-Bolyai University400084 Cluj-NapocaRomania Department of Geosciences The University of Arizona1040 E.4th StreetTucsonAZ 85721USA Faculty of Geology and Geophysics Bucharest UniversityStr.N.Balcescu Nr 1BucurestiRomania Institut fr Geowissenschaften Universitt Tbingen72076 TbingenGermany

The basement of the Romanian Carpathians is made of Neoproterozoic to early Paleozoic peri- Gondwanan terranes variably involved in the Variscan orogeny, similarly to other basement terrains of Europe. They were hardly dismembered during the Alpine orogeny and traditionally have their own names in the three Carpathian areas. The Danubian domain of the South Carpathians comprises the Dragsan and Lainici-Paiius peri-Amazonian terranes. The Dragsan terrane originated within the ocean surrounding Rodinia and docked with Rodinia at -800 Ma. It does not contain Cadomian magmatism and consequently it is classified as an Avalonian extra-Cadomian terrane, The Lainici-Pfiius terrane is a Ganderian fragment strongly modified by Cadomian subduction-related magmatism, It is attached to the Moesia platform. The TisoviD terrane is an ophiolite that marks the boundary between Drfagsan and Lainici-Paius terranes. The other basement terranes of the Romanian Carpathians originated close to the Ordovician North- African orogen, as a result of the eastern Rheic Ocean opening and closure. Except for the Sebes-Lotru terrane that includes a lower metamorphic unit of Cadomian age, all the other terranes （Bretila, Tulghes, Negrisoara and Rebra in the East Carpathians, Somes, Biharia and Baia de Aries in the Apuseni mountains, Fagaras, Leaota, Carat and Pades in the South Carpathians） represent late Cambrian-Ordovician rock assemblages. Their provenance, is probably within paleo-nortbeast Africa, close to the Arabian-Nubian shield. The late Cambrian-Ordovician terranes are defined here as Carpathian-type terranes. According to their lithostratigraphy and origin, some are of continental margin magmatic arc setting, whereas others formed in rift and back-arc environment and closed to passive continental margin settings. In a paleo- geographic reconstruction, the continental margin magmatic arc terranes were first that drifted out, followed by the passive continental margin terranes with the b

关键词： Romanian Carpathians pre-Alpine terranes U-Pb Geochronology Avalonian-type and Carpathian-type terranes Tornquist Rheic and Paleotethyan sutures Ordovician North-African orogen