Z Gastroenterol 2012; 50 - K066
DOI: 10.1055/s-0032-1324001

Thyroid dysfunction induced by peginterferon alfa-2b (Peg-2b)/Ribavirin (RBV) is a favorable predictor of SVR in difficult-to-treat patients with HCV Genotype 1 (G1) infection

S Mauss 1, D Hueppe 2, E Zehnter 3, MP Manns 4, G Teuber 5, T Dahhan 6, U Meyer 7, T Witthoeft 8, B Moeller 7, N Dikopoulos 9, J Brack 10, D Hartmann 11 M Bilzer 11, the bng hepatitis study group
  • 1Medical Group Practice, Düsseldorf, Germany
  • 2Medical Group Practice, Herne, Germany
  • 3Gastroenterological Practice, Dortmund, Germany
  • 4Medical High School Hannover, Hannover, Germany
  • 5Johann Wolfgang Goethe University, Frankfurt, Germany
  • 6Medical Practice, Fellbach, Germany
  • 7Medical Practice, Berlin, Germany
  • 8Gastroenterologische Facharztpraxis, Stade, Germany
  • 9Gesundheitszentrum Langenau, Langenau, Germany
  • 10Hospital Nord Ochsenzoll, Hamburg, Germany
  • 11MSD Pharma GmbH, Haar, Germany

Aims: Thyroiditis leading to thyroid dysfunction in up to 15% of pts treated for chronic HCV infection has been attributed to interferon-stimulated immune mechanisms similar to that in antiviral response induced by interferons. We analyzed the possible association between thyroid dysfunction related to Peg2b/RBV and the virologic outcome of pts treated for HCV G1 infection.

Methods: Data from 1923 pts treated for G1 infection with Peg2b 1.5µg/kg/wk+weight-based RBV 800–1200mg/day for up to 48 wks in an observational real-life study at 285 sites in Germany were retrospectively analyzed. Thyroid dysfunction was estimated by serum TSH levels. Pts who discontinued for non-response or for any other reasons were included in the analysis.

Results: 1436 pts had normal TSH levels at baseline and at least one TSH measurement during therapy. After starting treatment abnormal TSH values became apparent in 304 pts (21.2%). Compared to pts with normal TSH values significantly higher SVR rates were achieved by pts with abnormal TSH values. This favorable effect was more pronounced in „difficult-to-treat” pts with high baseline viral load (HVL) and age older than 50yrs and was associated with a significant reduction of virologic non-response. Similar and significant reductions of non-response rates were observed in pts with abnormal TSH values and low platelet count <150 n/L indicative for advanced fibrosis. Interestingly, SVR rate was not improved in this subgroup, but there was a shift from virologic non-response to relapse indicated by an increase of relapse rates from 31.1% to 45.0% in pts with normal/abnormal TSH values and low platelet count. Multivariate logistic regression analysis including gender, viral load, age and platelet count identified abnormal TSH as independent factor associated with SVR (OR=1.4; p=0.0124).

Table 1: SVR and non-response TSH

normal TSH

abnormal TSH

P

SVR, % (n/N)

overall

44.0 (498/1132)

53.6 (163/304)

0.0028

age <50 years

48.1 (361/750)

54.2 (117/216)

0.1181

age >50 years

35.9 (137/382)

52.3 (46/88)

0.0044

LVL <600.000 IU/ml

56.4 (286/507)

58.7 (84/143)

0.6191

HVL >600.000 IU/ml

33.6 (200/596)

49.0 (77/157)

0.0003

nonresponse, % (n/N)

overall

34.9 (395/1132)

24.7 (75/304)

0.0007

age <50 years

31.2 (234/750)

22.7 (49/216)

0.0154

age >50 years

42.1 (161/382)

29.5 (26/88)

0.0295

LVL <600.000 IU/ml

24.1 (122/507)

21.0 (30/143)

0.4416

HVL >600.000 IU/ml

44.0 (262/596)

27.4 (43/157)

0.0002

Conclusions: Thyroid dysfunction triggered during Peg2b/RBV treatment of HCV G1 infection is a favorable independent factor predicting high SVR and low non-response rates in difficult-to-treat pts.