Efficacy of telbivudine in the treatment of chronic hepatitis b and liver cirrhosis and its effect on immunological responses

Nan Meng , Xiao Gao , Wei Yan , Mi Wang , Ping Liu , Xiao-dan Lu , Shu-juan Zhang , Ya-qi Lu , Wang-xian Tang

Current Medical Science ›› 2015, Vol. 35 ›› Issue (2) : 230 -234.

PDF
Current Medical Science ›› 2015, Vol. 35 ›› Issue (2) : 230 -234. DOI: 10.1007/s11596-015-1416-3
Article

Efficacy of telbivudine in the treatment of chronic hepatitis b and liver cirrhosis and its effect on immunological responses

Author information +
History +
PDF

Abstract

This study was aimed to evaluate the long-term effects of telbivudine (LdT) in the treatment of chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) and to observe the changes of immunological responses during LdT treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with LdT for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen (HBeAg) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after LdT treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid (HA), human laminin (LN), human type IV collagen (IV-C) and human N-terminal procollagen III peptide (PC-III), were detected before and after LdT treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with LdT for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, LdT treatment led to the fluctuation of the circulating interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels at different time points in CHB group. It was concluded that LdT could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during LdT therapy.

Keywords

chronic hepatitis B / liver cirrhosis / telbivudine / interferon-γ / interleukin-10

Cite this article

Download citation ▾
Nan Meng, Xiao Gao, Wei Yan, Mi Wang, Ping Liu, Xiao-dan Lu, Shu-juan Zhang, Ya-qi Lu, Wang-xian Tang. Efficacy of telbivudine in the treatment of chronic hepatitis b and liver cirrhosis and its effect on immunological responses. Current Medical Science, 2015, 35(2): 230-234 DOI:10.1007/s11596-015-1416-3

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

LavanchyD. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat, 2004, 11(2): 97-107 PMID: 14996343

[2]

LuoZ, XieY, DengM, et al. . Prevalence of hepatitis B in the southeast of China: a population-based study with a large sample size. Eur J Gastroenterol Hepatol, 2011, 23(8): 695-700 PMID: 21617533

[3]

TanakaM, KatayamaF, KatoH, et al. . Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. J Epidemiol, 2011, 21(6): 401-416 PMCID: 3899457 PMID: 22041528

[4]

McMahonBJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis, 2005, 25(Suppl1): 3-8 PMID: 16103976

[5]

ZhuXF, LuLX, WangY, et al. . Effect and predictive elements for 52 weeks’ telbivudine treatment on naive HBeAg positive chronic hepatitis B. Hepat Mon, 2011, 11(12): 980-985 PMCID: 3282031 PMID: 22368682

[6]

PollicinoT, BellinghieriL, RestucciaA, et al. . Hepatitis B virus (HBV) induces the expression of interleukin-8 that in turn reduces HBV sensitivity to interferon-alpha. Virology, 2013, 444(1–2): 317-328 PMID: 23890815

[7]

LokAS, McMahonBJ. Chronic hepatitis B. Hepatology, 2001, 34(6): 1225-1241 PMID: 11732013

[8]

JungMC, PapeGR. Immunology of hepatitis B infection. Lancet Infect Dis, 2002, 2(1): 43-50 PMID: 11892495

[9]

KaoJH, ChenDS. Global control of hepatitis B virus infection. Lancet Infect Dis, 2002, 2(7): 395-403 PMID: 12127351

[10]

KondoY, AsabeS, KobayashiK, et al. . Recovery of functional cytotoxic T lymphocytes during lamivudine therapy by acquiring multi-specificity. J Med Virol, 2004, 4(3): 425-433

[11]

FengH, ZhangJ, LiX, et al. . HBX-mediated migration of HBV-replicating HepG2 cells: insights on development of hepatocellular carcinoma. J Biomed Biotechnol, 2009, 2009: 930268 PMCID: 2744885 PMID: 19763277

[12]

GaneEJ, WangY, LiawYF, et al. . Efficacy and safety of prolonged 3-year telbivudine treatment in patients with chronic hepatitis B. Liver Int, 2011, 31(5): 676-684 PMID: 21457439

[13]

LaiCL, GaneE, LiawYF, et al. . Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med, 2007, 357(25): 2576-2588 PMID: 18094378

[14]

LiawYF. On-treatment outcome prediction and adjustment during chronic hepatitis B therapy: now and future. Antivir Ther, 2009, 14(1): 13-22 PMID: 19320233

[15]

PhillipsMG, PreedyVR, HughesRD. Assessment of prognosis in alcoholic liver disease: can serum hyaluronate replace liver biopsy?. Eur J Gastroenterol Hepatol, 2003, 15(9): 941-944 PMID: 12923364

[16]

CadranelJF, RufatP, DegosF. Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology, 2000, 32(3): 477-481 PMID: 10960438

[17]

MaharajB, MaharajRJ, LearyWP, et al. . Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet, 1986, 1(8480): 523-525 PMID: 2869260

[18]

NordHJ. Biopsy diagnosis of cirrhosis: blind percutaneous versus guided direct vision techniques—a review. Gastrointest Endosc, 1982, 28(2): 102-104 PMID: 6211383

[19]

PiccininoF, SagnelliE, PasqualeG, et al. . Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J Hepatol, 1986, 2(2): 165-173 PMID: 3958472

[20]

CadranelJF, MathurinP. Prothrombin index decrease: a useful and reliable marker of extensive fibrosis?. Eur J Gastroenterol Hepatol, 2002, 14(10): 1057-1059 PMID: 12362094

[21]

CroquetV, VuilleminE, TernisienC, et al. . Prothrombin index is an indirect marker of severe liver fibrosis. Eur J Gastroenterol Hepatol, 2002, 14(10): 1133-1141 PMID: 12362105

[22]

ObertiF, ValsesiaE, PiletteC, et al. . Noninvasive diagnosis of hepatic fibrosis or cirrhosis. Gastroenterology, 1997, 113(5): 1609-1616 PMID: 9352863

[23]

PlevrisJN, HaydonGH, SimpsonKJ, et al. . Serum hyaluronan—a non-invasive test for diagnosing liver cirrhosis. Eur J Gastroenterol Hepatol, 2000, 12(10): 1121-1127 PMID: 11057458

[24]

GuechotJ, PouponRE, GiralP, et al. . Relationship between procollagen III aminoterminal propeptide and hyaluronan serum levels and histological fibrosis in primary biliary cirrhosis and chronic viral hepatitis C. J Hepatol, 1994, 20(3): 388-393 PMID: 8014451

[25]

RauchI, MullerM, DeckerT. The regulation of inflammation by interferons and their STATs. JAKSTAT, 2013, 2(1): e23820 PMCID: 3670275 PMID: 24058799

[26]

BonorinoP, RamzanM, CamousX, et al. . Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C. J Hepatol, 2009, 51(3): 458-467 PMID: 19596474

[27]

DunnC, BrunettoM, ReynoldsG, et al. . Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med, 2007, 204(3): 667-680 PMCID: 2137916 PMID: 17353365

[28]

OlivieroB, VarchettaS, PaudiceE, et al. . Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology, 2009, 137(3): 1151-1160 PMID: 19470388

[29]

ZhangZ, ZhangS, ZouZ, et al. . Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patients. Hepatology, 2011, 53(1): 73-85 PMCID: 3767982 PMID: 21254163

[30]

JiangY, MaZ, XinG, et al. . Th1 and Th2 immune response in chronic hepatitis B patients during a long-term treatment with adefovir dipivoxil. Mediators Inflamm, 2010, 2010: 143026 PMCID: 2994066 PMID: 21127728

[31]

GaetaGB, StornaiuoloG. Therapy of chronic hepatitis B: focus on telbivudine. Dig Liver Dis, 2007, 39(Suppl3): S372-S378 PMID: 18063258

[32]

DasA, MainiMK. Innate and adaptive immune responses in hepatitis B virus infection. Dig Dis, 2010, 28(1): 126-132 PMID: 20460900

[33]

ZhengY, HuangZ, ChenX, et al. . Effects of telbivudine treatment on the circulating CD4(+) T-cell subpopulations in chronic hepatitis B patients. Mediators Inflamm, 2012, 2012: 789859 PMCID: 3337496 PMID: 22570512

[34]

ShiTD, ZhangJM, WangXF, et al. . Effects of antiviral therapy with telbivudine on peripheral iNKT cells in HBeAg(+) chronic hepatitis B patients. Clin Exp Med, 2012, 12(2): 105-113 PMID: 21748522

[35]

ZhaoJ, LiY, JinL, et al. . Natural killer cells are characterized by the concomitantly increased interferon-gamma and cytotoxicity in acute resolved hepatitis B patients. PLoS One, 2012, 7(11): e49135 PMCID: 3486810 PMID: 23133672

[36]

AlatrakchiN, KozielM. Regulatory T cells and viral liver disease. J Viral Hepat, 2009, 16(4): 223-229 PMID: 19222744

[37]

CottrezF, GrouxH. Specialization in tolerance: innate CD(4+)CD(25+) versus acquired TR1 and TH3 regulatory T cells. Transplantation, 2004, 77(1Suppl): S12-S15 PMID: 14726762

[38]

StoopJN, van der MolenRG, BaanCC, et al. . Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology, 2005, 41(4): 771-778 PMID: 15791617

[39]

NanXP, ZhangY, YuHT, et al. . Inhibition of viral replication downregulates CD4(+)CD25(high) regulatory T cells and programmed death-ligand 1 in chronic hepatitis B. Viral Immunol, 2012, 25(1): 21-8 PMCID: 3271372 PMID: 22233255

AI Summary AI Mindmap
PDF

115

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/