|
E1E1. Weich V, Herrmann E, Chung TL, Sarrazin C, Hinrichsen H, Buggisch P, Gerlach T, Klinker H, Spengler U, Bergk A, Zeuzem S, Berg T. The determination of GGT is the most reliable predictor of nonresponsiveness to interferon-alpha based therapy in HCV type-1 infection. J Gastroenterol. 2011;46(12):1427-36. - The determination of GGT is the most reliable predictor of non responsiveness to interferon-alpha based therapy in HCV type-1 infection |
| Weich et al. (2011) |
G1
(n=561)
G2/3
(n=71) |
PEG IFN α2a 180 μg/week and α2b 1.5 μg/kg/week + RBV 800 at 1200 mg/day/24 to 48 weeks. |
Predictive power of the GGT level to SVR - correlation with several isolated variables, age and virological load; association of the binary variables, age (≤40 vs >40 years), presence or absence of severe fibrosis or cirrhosis; association among GGT low levels and ALT high base levels.
GGT < ULN: associated with best virologic response (SVR and EVR) at G1 (P<0.0001); predictive GGT regardless SVR: Multivariate logistic regression identified low GGT (P<0.0001), high ALT (P<0.0006), low viremia (P<0.0014), RVS independent predictors. This predictive factor may improve infection individualized theraphy; HCV G1; SVR n=371; 58.7%; ETR n= 115; 18.2%; NR n=146; 23.1%. |
|
E2E2. Kurosaki M, Matsunaga K, Hirayama I, Tanaka T, Sato M, Yasui Y, Tamaki N, Hosokawa T, Ueda K, Tsuchiya K, Nakanishi H, Ikeda H, Itakura J, Takahashi Y, Asahina Y, Higaki M, Enomoto N, Izumi N. A predictive model of response to peginterferon ribavirin in chronic hepatitis C using classification and regression tree analysis. Hepatol Res. 2010;40(4):251-60. - A predictive model of response to peginterferon Ribavirin in chronic hepatitis C using classification and regression tree analysis |
| Kurosaki et al. (2010) |
G1
(n=400) |
PEG-IFN α2b 1.5 μg/kg/week + RBV 60 mg <60 Kg; 800 mg 60-80 Kg; 1000 mg >80 Kg/day/24 toa 48 weeks
CART; The Classification and Regression Tree used to evaluate baseline predictors of response to treatment PEG-IFN/RBV among the clinic, biochemical, virologic and histological to define the pre treatment algorithm and discriminate patients who are likely responders.
Model n=269; Validation n=131 |
Low GGT-RVR/EVR predictor. Performed univariate logistic regression analysis (P<0.004) and multivariate logistic regression (P<0.005) showed significance for GGT <40 vs ≥40; low GGT predictor of the likelihood of RVR/RVPc (60% vs 35%), with 46% ratio for RVR/EVR. Estimates for SVR. |
|
E3E3. Mauss S, Hueppe D, John C, Goelz J, Heyne R, Moeller B, Link R, Teuber G, Herrmann A, Spelter M, Wollschlaeger S, Baumgarten A, Simon KG, Dikopoulos N, Witthoeft T. Estimating the likelihood of sustained virological response in chronic hepatitis C therapy. J Viral Hepat. 2011;18(4):e81-90. - Estimating the likelihood of sustained virological response in chronic hepatitis C therapy |
| Mauss et al. (2011) |
G1
G2
G3
G4
(n=2,378) |
PEG-IFN α2a ande α2b
Associated with RBV
PRACTICE: Pegylated interferon and Ribavirin: analysis of chronic hepatitis C treatment in centres of excellence. |
GGT normal vs >ULN (>66 U/L/Male; >35U/L/female). GGT normal (n=1094; 62%) significantly higher SVR compared GGT>ULN (n=822; 41.2%) in univariate logistic regression (P<0.001). SVR significantly associated with GGT.
In univariate analysis n=1377 (57.9%) achieved an SVR (P<0.001). Review of G1 / 4 (n=1496) SVR rate 46.5%; G2 / 3 (n=882) rate was 77.3% (P<0.001). GGT>ULN, age >40 years - negative predictors of SVR in multivariate analysis. Positive predictors SVR - multivariate analysis G2, G3 and low viral load; PEG-IFN α2a treatment is a positive predictor of SVR compared with PEG-IFN α2b. |
|
E4E4. Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, Wiedenmann B, Hopf U, Zeuzem S. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology. 2003;37(3):600-9. - Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy |
| Berg et al. (2003) |
G1
G2
G3
G4
G6
(n=260) |
PEG-IFN α2a 180 μg/week and α2b 1.0-1.5 μg/kg/week + RBV 800 toa 1200 mg/day/24 to 48 weeks.
IFN α2a and α2b; PEG-IFN α2a. |
Low levels of GGT significantly associated with SVR by univariate analysis (P<0.0001).
For multivariate analysis G2 n=21; 8.1% and G3 n=58, 22.2% (P<0.0001), low levels of GGT (P<0.0001) and levels of ALT (P=0.0002), were considered independent predictors of SVR.
SVR n=140/260, 53.8% ETR n=38; NR 14.6% n=82, 31.5%. |
|
E5E5. Kronenberger B, Herrmann E, Micol F, Von Wagner M, Zeuzem S. Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels. Hepatology. 2004;40(6):1442-9. - Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels |
| Kronenberger et al. (2004) |
G1
G2
G3
(n=39) |
PEG-IFN α2a 180 μg/1x/week + RBV 800-1200 mg/24 to 48 weeks |
Normal GGT levels: associated with greater loss of infected cells before treatment (P=0.005).
GGT high: association with reduced efficacy of blocking virus production and less loss of the infected cell. ULN/GGT: 52UI/L/masc; 33UI/L/fem.
Normal basal levels of GGT greater loss of infected cells during treatment compared with baseline levels of GGT levels (P=0.02).
GGT levels were significantly lower in SVR compared to NR 24 weeks after completion of therapy (P=0.002) |
|
E6E6. Kurosaki M, Sakamoto N, Iwasaki M, Sakamoto M, Suzuki Y, Hiramatsu N, Sugauchi F, Yatsuhashi H, Izumi N. Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis. J Gastroenterol. 2011;46(3):401-9. - Pretreatment prediction of response to peginterferon plus Ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis |
| Kurosaki et al. (2011) |
G1
(n=800) |
PEG-IFN α2b 1.5 μg/kg/SC/week/RBV 600 mg-60 kg, 800 mg 60-80 kg, 1000 mg >80kg/day/24 to 48 weeks.
Decision tree model: n=506; Validation n=294.
Developed to predict RVS at PEG-IFN and RBV. |
By multivariate analysis GGT is associated with SVR P=0.005.
Factors associated with SVR, GGT <40IU/L associated with SVR.
GGT independently associated with SVR.
Pac. with low levels of GGT higher probability of SVR (57% vs 34%) SVR rate ranging from 22% to 77%. |
|
E7E7. Çoban S, Idilman R, Erden E, Tüzün A. Gamma-glutamyltranspeptidase in predicting sustained virological response in individuals with chronic hepatitis C. Hepatogastroenterology. 2011;58(109):1301-6. - Gamma-glutamyltranspeptidase in predicting sustained virological response in individuals with chronic hepatitis C |
| Çoban et al. (2011) |
SI
(n=112) |
PEG-IFN α2b 1.5 μg/kg/week RBV 800 to 1200 mg/day, (<65 kg, 800 mg/day; 65-85 kg, 1000 mg/day; >85 kg 1200 mg/day). During 12 months. |
Low levels of GGT before treatment: associated with high rates of SVR
Normal GGT predictor of SVR.
SVR: n=64/112; 57.2% (combination therapy).
Factors associated with SVR: lower in patients with elevated GGT levels than in those with normal GGT (44.8% vs 70.4%).
SVR>GGT Normal Group (n=38/54, 70.4%) than in Group GGT>50IU/mL (n=26/58, 44.8%) P=0.0098 and GGT>100 (n=9/26, 34.6%) P=0.0018 - Analysis of multivariate regression. |
|
E8E8. Durante-Mangoni E, Zampino R, Portella G, Adinolfi LE, Utili R, Ruggiero G. Correlates and prognostic value of the first-phase hepatitis C virus RNA kinetics during treatment. Clin Infect Dis. 2009; 49(4):498-506. - Correlates and prognostic value of the first-phase hepatitis C virus RNA kinetics during treatment |
| Durant-Mangoni et al. (2009) |
G1n=61
G2n=44
G3n=14
(n=119) |
PEG-IFN α2a 180 μg/week or PEG-IFN alfa-2b 1.5 μg/kg/week.
Combined RBV 800 mg/day (400 mg twice /day) for G2 or G3; 1000 or 1200 mg/day for G1<75 ou ≥75 kg, respectively. G1 48 week. and G2/G3 24 weeks |
GGT levels (P<0.001) and RVR (P<0.001) are among the factors significantly associated with SVR by univariate analysis.
GGT: an independent predictor of SVR in the first phase of viral response through multivariate regression analysis
SVR: n=67/119; 56.3% NR: n=29/119; Relapse 24.4%: n=23; 19.3%. |
|
E9E9. Berg T, Von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, Goeser T, Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth U, and Zeuzem S. Extended Tratment Duration for Hepatitis C Virus Type 1: Comparing 48 Versus 72 Weeks of Peginterferon - Alfa -2a Plus Ribavirin. Gastroenterology. 2006;130(4):1086-97. - Extended tratment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon - alfa -2a plus Ribavirin |
| Berg et al. (2006) |
G1
(n=455) |
PEG-IFN α2a 180 μg/1x/week+RBV 800 mg VO/day
Group A (n=230): 48 week; Group B (n=225): 72 weeks.
|
Groups A and B: GGT levels identified as independent predictors through multivariate regression analysis (P<0.001) and associates through univariate regression analysis (P<0.001) with SVR.
ETF and SVR in group A and group B were 71% vs 63% and 53% vs 54% respectively, without significant difference.
Extend the duration of treatment is not recommended in HCV G1 infection and should be reserved only for patients with slow virologic response, defined as HCV-RNA positive at week 12 but negative at week 24. |
|
E10E10. von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Häussinger D, Herrmann E, and Zeuzem S. Peginterferon-alfa-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005;129(2):522-7. - Peginterferon-alfa-2a (40KD) and Ribavirin for 16 or 24 Weeks in patients with genotype 2 or 3 chronic hepatitis C |
| Wagner et al. (2005) |
G2
(n=39; 26%)
G3
(n=113; 74%)
G2/3
(n=1; <1%)
(n=153) |
PEG-IFN α2a 180 μg/1x/week / SC + RBV 800-1200 mg/day/VO. RBV:
(≤65 kg: 800mg; 65-85 kg: 1000mg; >85 kg: 1200 mg).
|
RVR (HCV RNA <600IU/mL at week 4):
Group A: n=71; 16 weeks; ETR: 94%; SVR: 82%.
Group B: n=71; 24 weeks; ETR: 85%; SVR: 80%.
HCV RNA ≥600 IU/mL at week 4:
Group C: n=11/153; 7%; 24% weeks; ETR: 73%; SVR: 36%.
Low GGT level: independent predictor of SVR by multivariate regression analysis.
G2/G3 (low viral load): RVR - Treatment / 16 weeks; G3 (high viral load): Treatment. longer may be required. |
