抗病毒治疗对慢性乙型重型肝炎近期预后影响的分析
|
摘要
目的:回顾性的总结抗病毒治疗对慢性乙型重型肝炎近期预后的影响,以求改善和提高慢性乙型重症肝炎的治疗水平。方法:采用回顾性分析,收集从2000年到2008年就诊于新疆医科大学第一附属医院感染科的84例慢性乙型重型肝炎患者的临床资料,这些患者被分为抗病毒治疗组(44例)和对照组(40例)。抗病毒组在内科常规治疗基础上,加用核苷类药物抗病毒药物;对照组患者仅使用内科常规支持治疗。于治疗后2周、4周观察各项指标,并分析比较抗病毒治疗组与对照组患者生化指标、病毒转阴率、MELD评分、生存率,预期死亡率和实际死亡率等。结果:1)治疗后2周各项观察指标示:①治疗2周后两组的TBiL、PTA、INR均值差异均有显著统计学意义(P<0.05),其他各指标没有统计学差异(P>0.05)。②抗病毒治疗组治疗前后MELD评分差异有统计学意义(P<0.05),对照组治疗前后没有统计学差异(P>0.05)。抗病毒治疗组与对照组治疗后比较,MELD评分差异有统计学意义(△P<0.05)。③抗病毒治疗组MELD评分20～29分组的预期死亡率与实际死亡率,差异有统计学意义(P<0.05),其他评分段预期死亡率和实际死亡率差异没有统计学意义;对照组MELD评分各段预期死亡率与实际死亡率之间均没有统计学差异(P>0.05)。2)抗病毒治疗4周各项观察指标示:①治疗4周后治疗组与对照组相比病毒转阴率差异有显著统计学意义,P<0.05.②初始病毒载量≥105拷贝/ml与<105拷贝/ml组的患者相比生存率差异有统计学意义(P<0.05)③治疗4周后抗病毒组与对照组生存率差异有显著统计学意义(P<0.05)。④合并并发症的患者中两组生存率差异有统计学意义,P<0.05。结论:抗病毒治疗可以改善生化指标,提高病毒转阴率,降低MELD评分,提高生存率,改善慢性乙型重型肝炎的预后。
Objective: To explore the influence of short-term prognosis of chronic severe hepatitis B patients treated with nucleosides antiviral therapy. To improve the level of treatment in patients with chronic severe hepatitis B. Method: A retrospective analysis was performed in 84 patients with chronic severe hepatitis B who hospitalized in Department of Infectious Diseases, First Affiliated Hospital, Xinjiang Medical University during period of 2000-2008..A total of 84 patients were divided into antiviral therapy and control groups. 44 patients in antiviral therapy group were treated with nucleosides antiviral drugs besides routine supportive therapy.40 patients in control group were only applied with routine supportive therapy. To observe every index after 2 and 4 weeks, analysis the biochemical indicator, negative conversion rate of HBVDNA, MELD score, virus survival rate, predictive mortality and actuality mortality of two groups. Result: 1.After 2weeks treatment the indexs are as follow:①There are difference between two groups of TBiL? PTA?INR (P<0.05). Another indexs have no differences (P>0.05).②In antiviral therapy group, MELD score has significant difference between before and after treatment (P<0.05). Control group has no significant difference in MELD score between patients before treatment and after treatment (P>0.05) After 2 weeks treatment there were significant difference in MELD score between patients in antiviral therapy group and control group (△P<0.05).③After 2 week treatment, the antivival group which MELD score between 20 to 29, there are significant difference between predictive mortality and actuality mortality (P<0.05). There was no significant difference between predictive mortality and actuality mortality in other MELD score group of antivival group. In every MELD score section of control group, there was no significant difference between predictive mortality and actuality mortality after 2 week treatment. (P>0.05). 2. After 4 weeks treatment the indexs are as follow:①After 4 weeks treatment, there are significant difference in negative conversion rate of HBVDNA between two groups (P<0.05).②There are significant difference in incipient virus load between patients in≥105copies/ml group and<105 copies /ml group (P<0.05).③There are significant difference in the survival rate of patients between antiviral therapy group and control group (P<0.05).④There are significant difference in patients who have complication between antiviral therapy group and control group (P<0.05). Conclusion: Antiviral therapy can improve the biochemical indicator, increase the conversion rate of HBVDNA, depress the MELD score, increase the the survival rate, improve the prognosis of chronic severe hepatitis B.
Objective: To explore the influence of short-term prognosis of chronic severe hepatitis B patients treated with nucleosides antiviral therapy. To improve the level of treatment in patients with chronic severe hepatitis B. Method: A retrospective analysis was performed in 84 patients with chronic severe hepatitis B who hospitalized in Department of Infectious Diseases, First Affiliated Hospital, Xinjiang Medical University during period of 2000-2008..A total of 84 patients were divided into antiviral therapy and control groups. 44 patients in antiviral therapy group were treated with nucleosides antiviral drugs besides routine supportive therapy.40 patients in control group were only applied with routine supportive therapy. To observe every index after 2 and 4 weeks, analysis the biochemical indicator, negative conversion rate of HBVDNA, MELD score, virus survival rate, predictive mortality and actuality mortality of two groups. Result: 1.After 2weeks treatment the indexs are as follow:①There are difference between two groups of TBiL? PTA?INR (P<0.05). Another indexs have no differences (P>0.05).②In antiviral therapy group, MELD score has significant difference between before and after treatment (P<0.05). Control group has no significant difference in MELD score between patients before treatment and after treatment (P>0.05) After 2 weeks treatment there were significant difference in MELD score between patients in antiviral therapy group and control group (△P<0.05).③After 2 week treatment, the antivival group which MELD score between 20 to 29, there are significant difference between predictive mortality and actuality mortality (P<0.05). There was no significant difference between predictive mortality and actuality mortality in other MELD score group of antivival group. In every MELD score section of control group, there was no significant difference between predictive mortality and actuality mortality after 2 week treatment. (P>0.05). 2. After 4 weeks treatment the indexs are as follow:①After 4 weeks treatment, there are significant difference in negative conversion rate of HBVDNA between two groups (P<0.05).②There are significant difference in incipient virus load between patients in≥105copies/ml group and<105 copies /ml group (P<0.05).③There are significant difference in the survival rate of patients between antiviral therapy group and control group (P<0.05).④There are significant difference in patients who have complication between antiviral therapy group and control group (P<0.05). Conclusion: Antiviral therapy can improve the biochemical indicator, increase the conversion rate of HBVDNA, depress the MELD score, increase the the survival rate, improve the prognosis of chronic severe hepatitis B.
引文
[1]王融冰,周桂琴,江宇泳,等. 799例重型肝炎患者的临床病原学与实验室分析[J].中华肝脏病杂志, 2006, 13:6552657.
[2]陈瑞玲,罗瑞红,等. MELD评分对慢性重型乙型病毒性肝炎患者短期预后评价的价值[J].中山大学学报(医学科学版), 2006, 27:594-596.
[3]赵志新.重型肝炎预后因素的研究进展[J].广东医学, 2005, 26(9):1297-1298.
[4]刘素娟.重型肝炎的治疗进展[J].医学理论与实践. 2008, 21:1029-1030.
[5]顾长海,等. T细胞毒致乙型肝炎坏死机制[J],肝功能衰竭, 2002:153-154
[6]于晓燕.抗病毒治疗在乙型重型肝炎中的应用与评价[J].中国危重病急救医学. 2006, 18:444-445.
[7]崇雨田,林潮双.慢性重型病毒性肝炎的治疗体会[J].新医学, 2007, 38:217-219
[8]王艳.重症肝炎的治疗[J].临床内科杂志, 2008, 25:296-29
[9] Guicciard M E, Gores G J. Apoptosis:a mechanism of acute and chronic liver injury [J],Gut. 2005, 54:1024-1033
[10]赵志新.乙型病毒性肝炎相关晚期肝病的抗病毒治疗进展[J].新医学, 2006, 37:757-758.
[11] YoshibaM. Recent advances in the treatment of fulminant hepatitis B[J]. NipponR insho, 2004, 62:280-283.
[12] Schmilovitz-Weiss H, Ben-A ri Z, Sikule E, et al Lamivudine treatment for acute severe hepatitis B:apilot study[J]. Liver Int, 2004, 24:547-551.
[13] Han Y X, Xue R, Zhao W, et al. A ntiviral therapeutic efficacy of fo scarnet in hepatitis B virus infection[J]. A ntiviral Res, 2005, 68:147 153
[14]中华医学会肝病分会,中华医学会感染病学分会.联合制订慢性乙型肝炎防治指南[J].临床肝胆病学杂志, 2006, 22(1):8-10.
[15] Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease[J]. Hepatology, 2001, 33(2):464-470.
[16] Lisa MF, Michael RL, Predicting the prognosis of chronic liver disease:An evolution from Child to MELD[J]. Hepatology, 2001, 33(2):473-475.
[17] Nakashima H, Fumsyo N, Kubo N, et al . Double point mutation in the core promoter region of hepatitis B(HBV)genotype C maybe related to liver deterioration in patients with chronic HBV infection[J]. Gastroenterol Hepatol, 2004, 19(5):541-550
[18]程凤英.抗病毒治疗慢性重型乙型肝炎165例临床分析[J].临床内科杂志, 2008, 25:484-486.
[19] Asselah T, Ripault M P, Castelnau C, et al The current ststus of antiviral therapy of chronic hepatitis B[J]. Clim Virol, 2005, 34:s115-124.
[20] Zhu Yg1A clinical study of severe hepatitis t reated wit h a partial plasma exchange artificial liver support systan[J] Zhonghua Gan Zang Bing Zhi, 2006, 14(8):61626171
[21] Luo HT Liu QM . Tan JJ, et al. Observation on hybrid bioar ificial liver support systems in treating chronic sever hepatitisn a study of 60 cases[J]. Zhonghua Ganzangbing Zazhi, 2006, 14(3):205-209.
[22]谢青,桂红莲.肝衰竭的诊断和治疗[J].世界感染杂志, 2006, 6(1):4-8.
[23]郑学红,等.拉米夫定治疗慢性重症乙型肝炎的疗效观察及护理[J].护理实践与研究. 2008, 5:33.
[24] Bambha K, Kim WR, Kremers WK, et al. Predicting survival among patients listed for liver transplantation. an assessment of serial MELD measurements. Am[J]. Transplant, 2004, 4(11):1798-1804.
[25] Jaideep B, Vanitha S, Cindy B, et al. Racial differences in model for end-stage liver disease(MELD)scores, change in MELD(delta MELD)on the transplant list, and waiting times of liver transplant recipients in the United States[J]. Hepatology, 2005, 42(suppl):205A.
[26] Malinchoc M, Kamath PS, Gordon FI), et al. A model to predict poorsurvival in p atients undergoing transjugular intra hepaticporto systemic shunts Hepatology, 2000(H), 31(4):864-871.
[27] Freeman RB, Wiensner RH, Harper A, etal, The new liver allocation system;moving toward evidengce-based transplantation policy[J]. Liver Trans-plantation, 2002, 8:851-858.
[28] Botta F, Giannini E, Romagnoli P, et al. MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function:a European study[J]. Gut, 2003, 52(1):134-139.
[29]刘青,等.应用MELD系统预测慢性重型肝炎的预后及其治疗效果[J].中华医学杂志, 2005, 85:1773-1777.
[30]中华医学会感染病学分会重型肝病与人工肝学组.肝衰竭诊疗指南[J].国际流行病. 2006, 8:217-221
[31]拉米夫定临床应用专家组. 2004年拉米夫定临床应用专家共识[J].中华肝脏病杂志, 2004, 12(7):425-428.
[32] Tsang SW, Chan HL, Leung NW, et al, Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection[J].AlimentPharmacol Ther, 2001, 15(11):1737-1744.
[33] Chien RN, Lin CH, Liaw YF. The effect of lamivudine therapy in hepatic decompensation during acute enacerbation of chronic hepatitis B[J]. Hepatol, 2003, 38(3):322-327.
[34] Peters M, Hann HW, Martin P, et al . Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine- resistant chronic hepatitis B[J]. Gastroenterology, 2004, 126(1):91-101.
[35]赵永祥.恩替卡韦治疗慢性重型肝炎临床观察报告[J].中国医药导报. 2007, 4:115
[1] LOK AS, McMahon B J. Chronic hepatitis B:update of recommendations[J]. Hepatology, 2004;39:857-861.
[2] Van Damme P, Van Herck K. A review of the efficacy, immunogenicity and tolerability of a combined hepatitis A and B vaccine[J]. Expert Revaccines, 2004, 3:249-267.
[3] Kew MC. Geographical determainants of hepatitis disease burden[J]. 11th International Symposium on Viral Hepatitis &Liver disease Proceeding Book, 2004:216-221.
[4]梁晓峰,陈园生,王晓军,等.中国3岁以上人群乙型肝炎血清流行病学研究[J].中华流行病学杂志, 2005, 26:655-658.
[5] de Franchis R, Hadebgue A, Lau G, EASL international Consensus Conference on Hepatitis B. 13-14 September(long version) [J]. Hepatol, 2003, 39 Suppl 1:S3-S25.
[6] Yang HI, Lu SN, Liaw YF, Heoatitis B e antigen and risk of hepatocellular carcinoma. N Engl J Med, 2002, 347:168-174.
[7] van Zonneveld M, Honkoop P, Hansen B E. Long-term follow-up of alpha-Interferon treatment of patients with chronic hepatitis B[J]. Hepatology, 2004, 39(2):804-801
[8] Harrs JM, Martin NE, Modi M. Pegylation:a novel process for Modifying pharmacokinetics[J]. Clin Pharmacokinet, 2001, 40:539-551.
[9] Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitisB. N Engl J Med, 2005, 3 52:2682-2695.
[10] Marcellin P, Lau GKK, Bonino F, et al. Peginterferon Alfa-2a alone, Lamivudine alone, and the two in combination in patients with HBeAg negative chronic hepatitis B. N Engl J Med, 2004, 351:1206-1217.
[11] Janssen HL, van Zonneveld M, Senturk H, et al, Pegylated interferon alfa-2b alone or combination with lamivudine for HBeAg-positive chronic hepatitis B[J]:a randomised trial. lancet, 2005, 365(9454):123-129.
[12]程乾刚,赵海红,聚乙二醇干扰素a-2a治疗乙型肝炎肝硬化失代偿期临床研究[J].临床肝胆病杂志, 2007, 23(6):424.
[13]尘学兰,等.慢性乙型病毒性肝炎抗病毒治疗药物的选择[J].中国医药导报, 2008, 5:28-29.
[14] Amarapurkar DN, patel ND. Combination of peinterferon alpha-2b and lamivudine indifficult-to-treat chronic hepatitis B[J]. Hepatology, 2004, 39(2):804-810.
[15] KeeffeE B, Dieterich DT, Han SHB, et al. A treatment algorithm for the management of chronic hepatutis B virus infection in the United States:An update[J]. Cliniucal gastroenterology, 2006, 4:936- 962.
[16]胡启江,等.干扰素治疗低病毒载量慢性乙型肝炎的近期疗效观察[J].临床肝胆杂志, 2006, 22(4):292
[17] Colombatto P, Civitano L, Bizzarri R, et al. A multiphase model of the dynamics of HBV infection in HBeAg-negative patients during pegylated interferon-alpha2a, lamivudine and combination therapy[J]. Antivir Ther, 2006, 11(2):197-212.
[18] Lok A S, LaiC L, LeungN, et al. Long-terms safety of lamivudine treatment in patients with chronic hepatitis B[J]. Gastroenterology, 2 003, 125:1714 -1722.
[19] Schmilovitz-weiss H, Ben-Ari Z, Sikuler E, et al. Lamivudine treatment for acute sever hepatitis B:a pilot study[J]. Liver Int, 2004, 24(6):547-551.
[20] Hadziyannis S, Tassopoulos N, Chang TT, et al. Long-term adefovir dipivoxil treatment induces regression of liver fibrosis in patients with HBeAg-negative chronic hepatitis B:Result after 5 years of therapy[J]. Hepatology, 2005, 42:754A.
[21] Sulkowaki M S. Treatment algorithm for the management of hepatitis C in HIV-coinfected persons[J]. Hepatol, 2006, 44(suppll):s49-s55.
[22] Clinical Practice Guideline Panel. Management of chronic hepatitis B[J]. 2009, 50:227-242.
[23] Strader D B, Wright T, Thomas D L, et al. Diagnosis, management, a nd treatment of hepatitis C[J]. Hepatology, 2 004, 3 9:1 147-1171.
[24] Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease[J]. N Engl J Med, 2004, 351:1521一1531.
[25]梁树德, 5种抗病毒药物治疗慢性乙型肝炎的研究,应用预防医学, 2008,增刊:2.
[26]姚光弼,王宝恩,崔振宇,等.拉米夫定治疗慢性乙型肝炎三年疗效观察[J],中华内科杂志, 2003, 42:382-387.
[27] Marcellin P, Chang T T, Lim SG, et al. Adefovir dipivoxil for the treat-Ment of hepatitis B e antigen-positive chorinc hepatitis B. N Engj J Med, 2003, 348:808-816.
[28]陈菊梅,朱传琳,皇甫玉珊,等.阿德福韦酯治疗慢性乙型肝炎的临床观察[J].传染病信息, 2007, 20(1):51.
[29] Hadziyannis SJ, Tassopoulos NC, Hepathcote EJ, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepayiyis B[J]. N Engl J Med, 2003, 348(9):800-807.
[30] Hadziyannis S J, Tassopoulos NC, Heathcote EJ, et al. Long-termt herapy with adefovirdi pivoxil for HBeAg-negativec hronich epatitisB[J]. N Engl Med, 2005, 3 52:2673-2681.
[31] Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B[J]. N Engl J Med, 2006, 354:1001-1010.
[32] Leung N, Peng CY, Sollano L, et al. Entecavir results in high HBV-DNA reduction vs adefovir in chronically infected HBeAg(+)anti-viral na?ve adults:48 wk results[J]. EASL, 2007, Batcelona, Spain, Abstract 49.
[33] Benhamou Y, Fleury H, Trimoulet P, et al. Anti-hepatitis B virus efficacy of tenofovir disoproxil fumaratein Hiv-infected patients[J]. Hepatology, 2006, 43(3):548-555
[34] Sherman M, Yurdaydin C, Sollano J, et al. Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronichepatitis B[J]. Gasroenterology, 2006, 130(7):2039-2049.
[35] Colonno RJ, Rose R, Levine SM, et al. Emergence of entecavir resistant Hepatitis B virus after one year of therapy in phase I &Ⅲstudies is only observed in lamivudine refractory patients[J]. Hepatology, 2004, 40(4, Suppl 1):661A.
[36] Di Bisceglie AM, Lai CL, Gane E et al. Telbivudine Globe Trial:Maximal early HBV suppression is predictive of optimal two-year efficacy in nucleoside-treated hepatitis B patients[J]. Hepatology, 2006, 44;230-231
[37] Lai CL, Gane E, Chao-Wei H, et al. Two-Year results from the Globe Trial in patients with hepatitis B:Greater clinical and antiviral efficacy for Telbivudine(LDT)vs lamivudine[J]. Hepatology, 2006, 44(suppl):222A.
[38] Menne S, Cote PJ, Korba BE, et al. Antiviral effect of oral administration of tenofovir disoproxil fumarate in woodchucks with chronic woodchuck hepatitis virus infection. [J]. Antimicrob Agents Chemother, 2005, 49(7):2720-2728.
[39] Gish RG, Trinh H, Leung N, et al. Safety and antiviral of emtricitabine for the treatment of chronic hepatitis B infection:a two-year study[J]. Hepatol, 2005, 43(1):50-66.
[40] Lim SG, Ng TM, Kung N, et al. A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B[J]. Arch Intern Med, 2006, 166(1):49-56.
[41]潘赞红,卢诚震,赵桂,等.抗HBV新核苷类药物的临床研究评价[J].天津药学, 2007, 19(5):69-71.
[42] Korbo BE, Cate PJ, Menne S, et al. Clevudine therapy with vaccine inhibits progression of chronic hepatitis and delays onset of hepatocellular carcinoma inchronic woodchuck hapetitis virus infection[J]. Antivir Ther, 2004, 9(6):937-952
[43] Ono-Nita SK, Kato N, Shiratori Y, et al The polymerase L 528M mutation Cooperates with nucleotide bingding-site mutations, increasing hepatitis B virus replication and drag-resistance[J]. Clin Invest, 2001, 107:449.
[44]斯崇文.乙肝病毒耐药及防治策略[J],中国医学论坛报, 2007. B08.
[45]李志群,美国肝病研究学会慢性乙肝防治指南[J].中国医学论坛报, 2007: B08.
[2]陈瑞玲,罗瑞红,等. MELD评分对慢性重型乙型病毒性肝炎患者短期预后评价的价值[J].中山大学学报(医学科学版), 2006, 27:594-596.
[3]赵志新.重型肝炎预后因素的研究进展[J].广东医学, 2005, 26(9):1297-1298.
[4]刘素娟.重型肝炎的治疗进展[J].医学理论与实践. 2008, 21:1029-1030.
[5]顾长海,等. T细胞毒致乙型肝炎坏死机制[J],肝功能衰竭, 2002:153-154
[6]于晓燕.抗病毒治疗在乙型重型肝炎中的应用与评价[J].中国危重病急救医学. 2006, 18:444-445.
[7]崇雨田,林潮双.慢性重型病毒性肝炎的治疗体会[J].新医学, 2007, 38:217-219
[8]王艳.重症肝炎的治疗[J].临床内科杂志, 2008, 25:296-29
[9] Guicciard M E, Gores G J. Apoptosis:a mechanism of acute and chronic liver injury [J],Gut. 2005, 54:1024-1033
[10]赵志新.乙型病毒性肝炎相关晚期肝病的抗病毒治疗进展[J].新医学, 2006, 37:757-758.
[11] YoshibaM. Recent advances in the treatment of fulminant hepatitis B[J]. NipponR insho, 2004, 62:280-283.
[12] Schmilovitz-Weiss H, Ben-A ri Z, Sikule E, et al Lamivudine treatment for acute severe hepatitis B:apilot study[J]. Liver Int, 2004, 24:547-551.
[13] Han Y X, Xue R, Zhao W, et al. A ntiviral therapeutic efficacy of fo scarnet in hepatitis B virus infection[J]. A ntiviral Res, 2005, 68:147 153
[14]中华医学会肝病分会,中华医学会感染病学分会.联合制订慢性乙型肝炎防治指南[J].临床肝胆病学杂志, 2006, 22(1):8-10.
[15] Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease[J]. Hepatology, 2001, 33(2):464-470.
[16] Lisa MF, Michael RL, Predicting the prognosis of chronic liver disease:An evolution from Child to MELD[J]. Hepatology, 2001, 33(2):473-475.
[17] Nakashima H, Fumsyo N, Kubo N, et al . Double point mutation in the core promoter region of hepatitis B(HBV)genotype C maybe related to liver deterioration in patients with chronic HBV infection[J]. Gastroenterol Hepatol, 2004, 19(5):541-550
[18]程凤英.抗病毒治疗慢性重型乙型肝炎165例临床分析[J].临床内科杂志, 2008, 25:484-486.
[19] Asselah T, Ripault M P, Castelnau C, et al The current ststus of antiviral therapy of chronic hepatitis B[J]. Clim Virol, 2005, 34:s115-124.
[20] Zhu Yg1A clinical study of severe hepatitis t reated wit h a partial plasma exchange artificial liver support systan[J] Zhonghua Gan Zang Bing Zhi, 2006, 14(8):61626171
[21] Luo HT Liu QM . Tan JJ, et al. Observation on hybrid bioar ificial liver support systems in treating chronic sever hepatitisn a study of 60 cases[J]. Zhonghua Ganzangbing Zazhi, 2006, 14(3):205-209.
[22]谢青,桂红莲.肝衰竭的诊断和治疗[J].世界感染杂志, 2006, 6(1):4-8.
[23]郑学红,等.拉米夫定治疗慢性重症乙型肝炎的疗效观察及护理[J].护理实践与研究. 2008, 5:33.
[24] Bambha K, Kim WR, Kremers WK, et al. Predicting survival among patients listed for liver transplantation. an assessment of serial MELD measurements. Am[J]. Transplant, 2004, 4(11):1798-1804.
[25] Jaideep B, Vanitha S, Cindy B, et al. Racial differences in model for end-stage liver disease(MELD)scores, change in MELD(delta MELD)on the transplant list, and waiting times of liver transplant recipients in the United States[J]. Hepatology, 2005, 42(suppl):205A.
[26] Malinchoc M, Kamath PS, Gordon FI), et al. A model to predict poorsurvival in p atients undergoing transjugular intra hepaticporto systemic shunts Hepatology, 2000(H), 31(4):864-871.
[27] Freeman RB, Wiensner RH, Harper A, etal, The new liver allocation system;moving toward evidengce-based transplantation policy[J]. Liver Trans-plantation, 2002, 8:851-858.
[28] Botta F, Giannini E, Romagnoli P, et al. MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function:a European study[J]. Gut, 2003, 52(1):134-139.
[29]刘青,等.应用MELD系统预测慢性重型肝炎的预后及其治疗效果[J].中华医学杂志, 2005, 85:1773-1777.
[30]中华医学会感染病学分会重型肝病与人工肝学组.肝衰竭诊疗指南[J].国际流行病. 2006, 8:217-221
[31]拉米夫定临床应用专家组. 2004年拉米夫定临床应用专家共识[J].中华肝脏病杂志, 2004, 12(7):425-428.
[32] Tsang SW, Chan HL, Leung NW, et al, Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection[J].AlimentPharmacol Ther, 2001, 15(11):1737-1744.
[33] Chien RN, Lin CH, Liaw YF. The effect of lamivudine therapy in hepatic decompensation during acute enacerbation of chronic hepatitis B[J]. Hepatol, 2003, 38(3):322-327.
[34] Peters M, Hann HW, Martin P, et al . Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine- resistant chronic hepatitis B[J]. Gastroenterology, 2004, 126(1):91-101.
[35]赵永祥.恩替卡韦治疗慢性重型肝炎临床观察报告[J].中国医药导报. 2007, 4:115
[1] LOK AS, McMahon B J. Chronic hepatitis B:update of recommendations[J]. Hepatology, 2004;39:857-861.
[2] Van Damme P, Van Herck K. A review of the efficacy, immunogenicity and tolerability of a combined hepatitis A and B vaccine[J]. Expert Revaccines, 2004, 3:249-267.
[3] Kew MC. Geographical determainants of hepatitis disease burden[J]. 11th International Symposium on Viral Hepatitis &Liver disease Proceeding Book, 2004:216-221.
[4]梁晓峰,陈园生,王晓军,等.中国3岁以上人群乙型肝炎血清流行病学研究[J].中华流行病学杂志, 2005, 26:655-658.
[5] de Franchis R, Hadebgue A, Lau G, EASL international Consensus Conference on Hepatitis B. 13-14 September(long version) [J]. Hepatol, 2003, 39 Suppl 1:S3-S25.
[6] Yang HI, Lu SN, Liaw YF, Heoatitis B e antigen and risk of hepatocellular carcinoma. N Engl J Med, 2002, 347:168-174.
[7] van Zonneveld M, Honkoop P, Hansen B E. Long-term follow-up of alpha-Interferon treatment of patients with chronic hepatitis B[J]. Hepatology, 2004, 39(2):804-801
[8] Harrs JM, Martin NE, Modi M. Pegylation:a novel process for Modifying pharmacokinetics[J]. Clin Pharmacokinet, 2001, 40:539-551.
[9] Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitisB. N Engl J Med, 2005, 3 52:2682-2695.
[10] Marcellin P, Lau GKK, Bonino F, et al. Peginterferon Alfa-2a alone, Lamivudine alone, and the two in combination in patients with HBeAg negative chronic hepatitis B. N Engl J Med, 2004, 351:1206-1217.
[11] Janssen HL, van Zonneveld M, Senturk H, et al, Pegylated interferon alfa-2b alone or combination with lamivudine for HBeAg-positive chronic hepatitis B[J]:a randomised trial. lancet, 2005, 365(9454):123-129.
[12]程乾刚,赵海红,聚乙二醇干扰素a-2a治疗乙型肝炎肝硬化失代偿期临床研究[J].临床肝胆病杂志, 2007, 23(6):424.
[13]尘学兰,等.慢性乙型病毒性肝炎抗病毒治疗药物的选择[J].中国医药导报, 2008, 5:28-29.
[14] Amarapurkar DN, patel ND. Combination of peinterferon alpha-2b and lamivudine indifficult-to-treat chronic hepatitis B[J]. Hepatology, 2004, 39(2):804-810.
[15] KeeffeE B, Dieterich DT, Han SHB, et al. A treatment algorithm for the management of chronic hepatutis B virus infection in the United States:An update[J]. Cliniucal gastroenterology, 2006, 4:936- 962.
[16]胡启江,等.干扰素治疗低病毒载量慢性乙型肝炎的近期疗效观察[J].临床肝胆杂志, 2006, 22(4):292
[17] Colombatto P, Civitano L, Bizzarri R, et al. A multiphase model of the dynamics of HBV infection in HBeAg-negative patients during pegylated interferon-alpha2a, lamivudine and combination therapy[J]. Antivir Ther, 2006, 11(2):197-212.
[18] Lok A S, LaiC L, LeungN, et al. Long-terms safety of lamivudine treatment in patients with chronic hepatitis B[J]. Gastroenterology, 2 003, 125:1714 -1722.
[19] Schmilovitz-weiss H, Ben-Ari Z, Sikuler E, et al. Lamivudine treatment for acute sever hepatitis B:a pilot study[J]. Liver Int, 2004, 24(6):547-551.
[20] Hadziyannis S, Tassopoulos N, Chang TT, et al. Long-term adefovir dipivoxil treatment induces regression of liver fibrosis in patients with HBeAg-negative chronic hepatitis B:Result after 5 years of therapy[J]. Hepatology, 2005, 42:754A.
[21] Sulkowaki M S. Treatment algorithm for the management of hepatitis C in HIV-coinfected persons[J]. Hepatol, 2006, 44(suppll):s49-s55.
[22] Clinical Practice Guideline Panel. Management of chronic hepatitis B[J]. 2009, 50:227-242.
[23] Strader D B, Wright T, Thomas D L, et al. Diagnosis, management, a nd treatment of hepatitis C[J]. Hepatology, 2 004, 3 9:1 147-1171.
[24] Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease[J]. N Engl J Med, 2004, 351:1521一1531.
[25]梁树德, 5种抗病毒药物治疗慢性乙型肝炎的研究,应用预防医学, 2008,增刊:2.
[26]姚光弼,王宝恩,崔振宇,等.拉米夫定治疗慢性乙型肝炎三年疗效观察[J],中华内科杂志, 2003, 42:382-387.
[27] Marcellin P, Chang T T, Lim SG, et al. Adefovir dipivoxil for the treat-Ment of hepatitis B e antigen-positive chorinc hepatitis B. N Engj J Med, 2003, 348:808-816.
[28]陈菊梅,朱传琳,皇甫玉珊,等.阿德福韦酯治疗慢性乙型肝炎的临床观察[J].传染病信息, 2007, 20(1):51.
[29] Hadziyannis SJ, Tassopoulos NC, Hepathcote EJ, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepayiyis B[J]. N Engl J Med, 2003, 348(9):800-807.
[30] Hadziyannis S J, Tassopoulos NC, Heathcote EJ, et al. Long-termt herapy with adefovirdi pivoxil for HBeAg-negativec hronich epatitisB[J]. N Engl Med, 2005, 3 52:2673-2681.
[31] Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B[J]. N Engl J Med, 2006, 354:1001-1010.
[32] Leung N, Peng CY, Sollano L, et al. Entecavir results in high HBV-DNA reduction vs adefovir in chronically infected HBeAg(+)anti-viral na?ve adults:48 wk results[J]. EASL, 2007, Batcelona, Spain, Abstract 49.
[33] Benhamou Y, Fleury H, Trimoulet P, et al. Anti-hepatitis B virus efficacy of tenofovir disoproxil fumaratein Hiv-infected patients[J]. Hepatology, 2006, 43(3):548-555
[34] Sherman M, Yurdaydin C, Sollano J, et al. Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronichepatitis B[J]. Gasroenterology, 2006, 130(7):2039-2049.
[35] Colonno RJ, Rose R, Levine SM, et al. Emergence of entecavir resistant Hepatitis B virus after one year of therapy in phase I &Ⅲstudies is only observed in lamivudine refractory patients[J]. Hepatology, 2004, 40(4, Suppl 1):661A.
[36] Di Bisceglie AM, Lai CL, Gane E et al. Telbivudine Globe Trial:Maximal early HBV suppression is predictive of optimal two-year efficacy in nucleoside-treated hepatitis B patients[J]. Hepatology, 2006, 44;230-231
[37] Lai CL, Gane E, Chao-Wei H, et al. Two-Year results from the Globe Trial in patients with hepatitis B:Greater clinical and antiviral efficacy for Telbivudine(LDT)vs lamivudine[J]. Hepatology, 2006, 44(suppl):222A.
[38] Menne S, Cote PJ, Korba BE, et al. Antiviral effect of oral administration of tenofovir disoproxil fumarate in woodchucks with chronic woodchuck hepatitis virus infection. [J]. Antimicrob Agents Chemother, 2005, 49(7):2720-2728.
[39] Gish RG, Trinh H, Leung N, et al. Safety and antiviral of emtricitabine for the treatment of chronic hepatitis B infection:a two-year study[J]. Hepatol, 2005, 43(1):50-66.
[40] Lim SG, Ng TM, Kung N, et al. A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B[J]. Arch Intern Med, 2006, 166(1):49-56.
[41]潘赞红,卢诚震,赵桂,等.抗HBV新核苷类药物的临床研究评价[J].天津药学, 2007, 19(5):69-71.
[42] Korbo BE, Cate PJ, Menne S, et al. Clevudine therapy with vaccine inhibits progression of chronic hepatitis and delays onset of hepatocellular carcinoma inchronic woodchuck hapetitis virus infection[J]. Antivir Ther, 2004, 9(6):937-952
[43] Ono-Nita SK, Kato N, Shiratori Y, et al The polymerase L 528M mutation Cooperates with nucleotide bingding-site mutations, increasing hepatitis B virus replication and drag-resistance[J]. Clin Invest, 2001, 107:449.
[44]斯崇文.乙肝病毒耐药及防治策略[J],中国医学论坛报, 2007. B08.
[45]李志群,美国肝病研究学会慢性乙肝防治指南[J].中国医学论坛报, 2007: B08.