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| 1 | Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine显示文摘AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination. | Scott Bowden Stephen Locarnini Ting-Tsung Chang You-Chen Chao Kwang-Hyub Han Robert G Gish Robert A de Man Miao Yu Cyril Llamoso Hong Tang | 2015 | World Journal of Gastroenterology2015，21，15： | 11 |
| 2 | Targeted systemic therapies for hepatocellular carcinoma:Clinical perspectives,challenges and implications显示文摘Hepatocellular carcinoma(HCC) is a lethal disease in most patients,due to its aggressive course and a lack of effective systemic therapies for advanced disease.Surgical resection and liver transplantation remain the only curative options for a small subset of patients.Few patients with HCC are diagnosed early enough to be eligible for curative treatment.Angiogenesis inhibition is a natural therapeutic target for all solid tumors,but particularly for the highly vascularized HCC tumors.With the approval of the targeted agent sorafenib,there are now additional options for patients with HCC.Although sorafenib does produce some improvement in survival in HCC patients,the responses are not durable.In addition,there are significant dermatologic,gastrointestinal,and metabolic toxicities,and,as importantly,there is still limited knowledge of its usefulness in special subpopulations with HCC.Other angiogenesis inhibitors are in development to treat HCC both in the first-line setting and for use following sorafenib failure;the furthest in development is brivanib,a dual fibroblast growth factor pathway and vascular endothelial growth factor receptor inhibitor.Additional agents with antiangiogenic properties also in phase Ⅱ and Ⅲ development for the treatment of patients with HCC include bevacizumab,ramucirumab,ABT-869,everolimus and ARQ 197. | Catherine Frenette Robert Gish | 2012 | World Journal of Gastroenterology2012，18，6： | 10 |
| 3 | Classifying genotype F of hepatitis B virus into F1 and F2 subtypes显示文摘AIM: To explore the propriety of providing hepatitis B virus(HBV) genotypes F and H with two distinct genotypes.METHODS: Eleven HBV isolates of genotype F (HBV/F)were recovered from patients living in San Francisco,Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported.RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates,and differed by > 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of >8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged.CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H). | Hideaki Kato Kei Fujiwara Robert G. Gish Hiroshi Sakugawa Hiroshi Yoshizawa Fuminaka Sugauchi Etsuro Orito Ryuzo Ueda Yasuhito Tanaka Takanobu Kato Yuzo Miyakawa Masashi Mizokami | 2005 | World Journal of Gastroenterology2005，11，40： | 6 |
| 4 | American Gastroenterological Association Institute Technical Review on Prevention and Treatment of Hepatitis B Virus Reactivation During Immunosuppressive Drug Therapy显示文摘 | Robert P. Perrillo Robert Gish Yngve T. Falck-Ytter | 2015 | Gastroenterology2015，，： | 3 |
| 5 | A multicenter United States—Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B显示文摘 | Robert P. Perrillo Teresa Wright Jorge Rakela Gary Levy Eugene Schiff Robert Gish Paul Martin Jules Dienstag Paul Adams Rolland Dickson Gaya Anschuetz Steve Bell Lynn Condreay Nathaniel Brown | 2001 | Hepatology2001，，2： | 2 |
| 6 | Similar Risk of Renal Events Among Patients Treated With Tenofovir or Entecavir for Chronic Hepatitis B显示文摘 | Robert G. Gish Margaret D. Clark Steve D. Kane Richard E. Shaw Michael F. Mangahas Sumbella Baqai | 2012 | Clinical Gastroenterology and Hepatology2012，，8： | 2 |
| 7 | 恩替卡韦与拉米夫定治疗HBeAg阳性慢性乙型肝炎的比较显示文摘Background:Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus(HBV).Methods:In this phase 3,double-blind trial,we randomly assigned 715 patients with hepatitis B e antigen(HBeAg)positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks.The primary efficacy end point was histologic improvement(a decrease by at least two points in the Knodell necro-inflammatory score,without worsening of fibrosis)at week 48.Secondary end points included a reduction in the serum HBV DNA level,HBeAg loss and seroconversion,and normalization of the alanine aminotransferase level.Results:Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group(72 percent)and 195 of 314 patients in the lamivudine group(62 percent,P=0.009).More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay(67 percent vs.36 percent,P< 0.001)and normalization of alanine aminotransferase levels(68 percent vs.60 percent,P=0.02).The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine(6.9 vs.5.4 log on a base-10 scale copies per milliliter,P < 0.001).HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine(P=0.33).No viral resistance to entecavir was detected.Safety was similar in the two groups.Conclusions:Among patients with HBeAg-positive chronic hepatitis B,the rates of histologic,virologic,and biochemical improvement are significantly higher with entecavir than with lami vudine.The safety profile of the two agents is similar,and there is no evidence of viral resistance to entecavir. | Gish R.G. 王晓君 | 2006 | 世界核心医学期刊文摘(胃肠病学分册)2006，2，9： | 2 |
| 8 | Interleukin-6 and oncostatin M are elevated in liver disease inconjunction with candidate hepatocellular carcinoma biomarker GP73显示文摘 | Hongyan Liang Timothy M. Block Mengjun Wang Bradley Nefsky Ronald Long Julie Hafner Anand S. Mehta Jorge Marrero Robert Gish Pamela A. Norton | 2012 | Cancer Biomarkers2012，，4： | 2 |
| 9 | Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities显示文摘 | Robert G. Gish Bruce D. Given Ching-Lung Lai Stephen A. Locarnini Johnson Y.N. Lau David L. Lewis Thomas Schluep | 2015 | Antiviral Research2015，，： | 2 |
| 10 | Chronic Hepatitis B Infection显示文摘 | Alexander Kuo Robert Gish | 2012 | Clinics in Liver Disease2012，，2： | 2 |
| 11 | A dose- ranging study of the efficacy and tolerability of entecavir in lamivudine - refractory chronic hepatitis B patients 显示文摘 | Chang TT Gish RG Hadziyannis SJ | 2005 | Gastroenterlogy2005，129，8： | 1 |
| 12 | The discoindin domain receptor tyrosine kinases are activated by collagen 显示文摘 | Gish GD Alves F | 1997 | Mol Cell1997，1，1： | 1 |
| 13 | Text-Independent Speaker Identification显示文摘 | Gish H Schmid M | 1994 | IEEE Signal Processing Magazine1994，11，4： | 1 |
| 14 | A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B显示文摘 | CHANG T T GISH R G DE MAN R | 2006 | N Engl J Med2006，354，： | 1 |
| 15 | Dose range study of pharmacokinetics, safety, and preliminary antiviral activity of emtricitabine in adults with hepatitis B virus infection显示文摘 | Gish RG Leung NW Wright TL | 2002 | Antimicrob Agents Chemother2002，46，6： | 1 |
| 16 | Basic local alignment search tool显示文摘 | Ahschul S F Gish W Miller W | 1990 | J Mol Biol1990，215，3： | 1 |
| 17 | Immunoregulatory cytokinesin chronic hepatitis C virus infection:pre-and posttreatment with interferon alpha显示文摘 | Cacciarelli TV Martinez OM Gish RG | 1996 | Hepatology1996，24，1： | 1 |
| 18 | Groundwater-residues of atrazine, alachlor, and cyanazine under no-tillage practices 显示文摘 | Isensee A R Helling C S Gish T J | 1988 | Chemosphere1988，17，1： | 1 |
| 19 | Bcr-Abl oncoproteins binddirectly toactivators of the Ras signalling pathway显示文摘 | Puil L Liu J Gish G | 1994 | EMBO J1994，13，4： | 1 |
| 20 | 'Interview: Gish Jen' 显示文摘 | Matsukawa Yuko & Gish Jen | 1993 | MELUS: Asian Perspectives1993，，4： | 1 |
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