Studies published to date regarding on-treatment outcome prediction during chronic hepatitis B therapy were reviewed. Studies have shown that initial virological responses in terms of week 24 serum hepatitis B virus (HBV) DNA levels are associated with therapeutic outcomes of 1-year pegylated interferon-α and entecavir therapy, and weeks 52 or 104 of lamivudine and telbuvudine therapy. HBV DNA levels at week 48 are also associated with long-term adefovir therapy outcomes. Conceptual on-treatment adjustment and strategies have been proposed; however, this approach seems only necessary during therapy with nucleos(t)ide analogues with substantial risk of drug resistance. In addition, studies are needed to decide whether switching to or adding on a second drug, and with which drug, is the most cost-effective strategy.
References
1.
FosterG., MathurinP.Hepatitis C virus therapy to date.Antivir Ther2008; 13 Suppl 1: 3–8.
2.
LeeS.S., FerenciP.Optimizing outcomes in patients with hepatitis C virus genotype 1 or 4.Antivir Ther2008; 13 Suppl 1: 9–16.
3.
Asian Pacific Association for the Study of the Liver (APASL) Hepatitis C Working Party, McCaughan GW, Omata M, et al.Asian Pacific Association for the Study of the Liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection.J Gastroenterol Hepatol2007; 22: 615–633.
4.
LaiC.L., ChienR.N., LeungN.W.A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.N Engl J Med1998; 339: 61–68.
5.
HadziyannisS.J., TassopoulosN.C., HeathcoteE.J.Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B.N Engl J Med2003; 348: 800–807.
6.
MarcellinP., ChangT.T., LimS.G.Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B.N Engl J Med2003; 348: 808–816.
7.
LaiC.L., ShouvalD., LokA.S.Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B.N Engl J Med2006; 354: 1011–1020.
8.
ChangT.T., GishR.G., de ManR.A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.N Engl J Med2006; 354: 1001–1010.
9.
LaiC.L., GaneE., LiawY.F.Telbivudine versus lamivudine in patients with chronic hepatitis B.N Engl J Med2007; 357: 2576–2588.
10.
MarcellinP., LauG.K., BoninoF.Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B.N Engl J Med2004; 351: 1206–1217.
11.
LauG.K., PiratvisuthT., LuoK.X.Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.N Engl J Med2005; 352: 2682–2695.
12.
LiawY.F., LeungN., KaoJ.H.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update.Hepatol Int2008; 2: 263–283.
PiratvisuthT., LauG., ChaoY.C.Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.Hepatol Int2008; 2: 102–110.
15.
ChienR.N., YehC.T., TsaiS.L., ChuC.M., LiawY.F.Determinants for sustained HBeAg response to lamivudine therapy.Hepatology2003; 38: 1267–1273.
16.
DienstagJ.L., GoldinR.D., HeathcoteE.J.Histological outcome during long-term lamivudine therapy.Gastroenterology2003; 124: 105–117.
17.
HadziyannisS.J., TassopoulosN.C., HeathcoteE.J.Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years.Gastroenterology2006; 131: 1743–1751.
18.
LiawY.F., SungJ.J.Y., ChowW.C.Lamivudine for patients with chronic hepatitis B and advanced liver disease.N Engl J Med2004; 351: 1521–1531.
19.
HeathcoteE.J., GaneE.J., MarcellinP.Two year tenofovir disoproxil fumarate (TDF) treatment and adefovir dipivoxil (ADV) switch data in HBeAg-positive patients with chronic hepatitis B (study 103).Hepatology2008; 48 Suppl 1: 376A.
20.
TenneyD.J., PokornowskiK.A., RoseR.E.Entecavir at five years shows long-term maintenance of high genetic barrier to hepatitis B virus resistance.Hepatol Int2008; 2 Suppl 2: S76.
21.
van BömmelF., WünscheT., MaussS.Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection.Hepatology2004; 40: 1421–1425.
22.
LiawY.F., GaneE., LeungN.2-Year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B.Gastroenterology2009; 136: 486–495.
23.
RaptiI., DimouE., MitsoulaP., HadziyannisS.J.Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B.Gastroenterology2009; 45: 486–495.
24.
ShermanM., YurdaydinC., SimsekH.Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical, and serology outcomes through 96 weeks.Hepatology2008; 48: 99–108.
25.
ChienR.N., LiawY.F., AtkinsM.Pretherapy alanine transaminase level as a determinant for hepatitis B e antigen seroconversion during lamivudine therapy in patients with chronic hepatitis B.Hepatology1999; 30: 770–774.
26.
BoninoF., MarcellinP., LauG.K.K.Predicting response to peginterferon α-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B.Gut2007; 56: 699–705.
27.
HeijtinkR.A., JanssenH.L., HopW.C., OsterhausA.D., SchalmS. W.. Interferon-α therapy in chronic hepatitis B: early monitoring of hepatitis B e antigen may help to decide whether to stop or to prolong therapy.J Viral Hepat2000; 7: 382–386.
28.
FriedM.W., PiratvisuthT., LauG.K.K.HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B.Hepatology2008; 47: 428–434.
29.
ter BorgM.J., van ZonneveldM., ZeuzemS.Patterns of viral decline during PEG-interferon alpha-2b therapy in HBeAg-positive chronic hepatitis B: relation to treatment response.Hepatology2006; 44: 721–727.
30.
FarciP., MarcellinP., LuZ.M.On-treatment predictors of sustained biochemical and vriological response in patients with HBeAg-negative chronic hepatitis B (CHB) treated with peginterferon α-2a (40kD) (Pegasys®).J Hepatol2005; 42 Suppl 2: 175.
31.
ChanH.L., WongV.W., ChimA.M., WongG.L., ChanH.Y., SungJ.J.Treatment of patients with chronic hepatitis B who have failed previous antiviral treatment with pegylated interferon-α2a (40 kDa; PEGASYS®).Antivir Ther2008; 13: 555–562.
32.
ChanH.L., WongV.W., WongG.L., ChimA.M., ChanH.Y., SungJ.J.Early hepatitis B virus DNA suppression can predict virologic response to peginterferon and lamivudine treatment.Clin Gastroenterol Hepatol2008; 6: 1022–1026.
33.
LutgehetmannM., VolztT., QuaasA.Sequential combination therapy leads to biochemical and histological improvement despite low ongoing intrahepatic hepatitis B virus replication.Antivir Ther2008; 13: 57–66.
34.
LauG.K.K., MarcellinP., BrunettoM.On-treatment HBsAg decline during peginterferon alfa-2a (40KD) ±lamivudine in patients with HBeAg-positive CHB as a potential predictor of durable off-treatment response.Hepatology2008; 48 Suppl 1: 714A.
35.
MarcellinP., BrunettoM., BoninoF.In patients with HBsAg-negative chronic hepatitis B HBsAg serum levels early during treatment with peginterferon alfa-2a predict HBsAg clearance 4 years post-treatment.Hepatology2008; 48 Suppl 1: 718A.
36.
GauthierJ., BourneE.J., LutzM.W.Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine.J Infect Dis1999; 180: 1757–1762.
37.
ZöllnerB., SchäferP., FeuchtH.H., SchröterM., PetersenJ., LaufsR.Correlation of hepatitis B virus load with loss of e antigen and emerging drug-resistant variants during lamivudine therapy.J Med Virol2001; 65: 659–663.
38.
LaiC.L., LeungN., TeoE.K.A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B.Gastroenterology2005; 129: 528–536.
39.
ChanH.L., HeathcoteE.J., MarcellinP.Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial.Ann Intern Med2007; 147: 745–754.
40.
ChanH.L., WangH., NiuJ., ChimA.M., SungJ.J.Two-year lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B: a double-blind, placebo-controlled trial.Antivir Ther2007; 12: 345–353.
41.
YuenM.F., FongD.Y., WongD.K., YuenJ.C., FungJ., LaiC.L.Hepatitis B virus DNA levels at week 4 of lamivudine treatment predict the 5-year ideal response.Hepatology2007; 46: 1695–1703.
42.
HadziyannisA.S., MitsoulaP.V., HadziyannisS.J.Prediction of long-term maintenance of virologic response during lamivuidne treatment in HBeAg negative chronic hepatitis B.Hepatology2007; 46 Suppl 1: 667A.
43.
GallegoA., SheldonJ., García-SamaniegoJ.Evaluation of initial virological response to adefovir and development of adefovir-resistant mutations in patients with chronic hepatitis B.J Viral Hepat2008; 15: 392–398.
44.
PritchettS., WongD.K., YimC., MazzulliT., HeathcoteE.J.Factors affecting response to adefovir treatment in patients with chronic hepatitis B and lamivudine resistance.Hepatology2007; 46 Suppl 1: 675A.
45.
ParkN.H., ShinJ.W., ParkJ.W.Predictors of virologic response and resistance to adefovir in patients with lamivuidne-resistance chronic hepatitis B virus infection.Hepatology2007; 46 Suppl 1: 675A.
46.
HanW.S., YeonJ.E., KimY.H.Virologic response at treatment month 12 may predict sustained antiviral efficacy in adefovir treated lamivudine-resistant chronic hepatitis B.J Hepatol2007; 46 Suppl 1: S188.
HeathcoteJ., GeorgeJ., GordonS.Tenofovir disoproxil fulmarate (TDF) for the treatment of HBeAg-positive chronic hepatitis B: week 72 TDF data and week 24 adefovir dipivoxil switch data.J Hepatol2008; 48 Suppl 2: S32.
49.
YuenM.F., SablonE., HuiC.K., YuanH.J., DecraemerH., LaiC.L.Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy.Hepatology2001; 34: 785–791.
50.
LocarniniS., QiX., ArterburnS.Incidence and predictors of emergence of adefovir resistant HBV during four years of adefovir dipivoxil (ADV) therapy for patients with chronic hepatitis B (CHB).J Hepatol2005; 42 Suppl 2: 17.
51.
CastelH., OsiowyC., HeathcoteE.J., WillemsB., VilleneuveJ.P.Is viral load at week 48 predictive of adefovir resistance in HBV patients receiving adefovir for lamivudine resistance?J Hepatol2008; 48 Suppl 2: S255.
LauG., MarcellinP., PetersM.Chronic hepatitis B: a global health problem requiring coherent worldwide treatment strategies.Hepatol Int2007; 1: 316–325.
54.
GishR.G., LokA.S., ChangT.T.Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B.Gastroenterology2007; 133: 1437–1444.
55.
WiegandJ., HasencleverD., TillmannH.L.Should treatment of hepatitis B depend on hepatitis B virus genotypes? A hypothesis generated from an explorative analysis of published evidence.Antivir Ther2008; 13: 211–220.
56.
HwangS.G., GaneE., SafadiR.Telbivudine versus lamivudine in lamivudine experienced patients: primary analysis at week 24.Hepatol Int2007; 1: 14.
57.
TanJ., DegertekinB., WongS.N., HusainM., OberhelmanK., LokA.S.F.Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations.J Hepatol2008; 48: 391–398.
58.
KeeffeE.B., ZeuzemS., KoffR.S.Report of an international workshop: roadmap for management of patients receiving oral therapy for chronic hepatitis B.Clin Gastroenterol Hepatol2007; 5: 890–897.
