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259 ANTIVIRAL EFFICACY OF RIBAVIRIN MONOTHERAPY FOLLOWED BY STANDARD COMBINATION TREATMENT IN CHRONIC HEPATITIS C
POSTERS (IP-10 or CXCL10) level might be a predictive factor for sustained virological response (SVR) to pegylated IFN plus ribavirin (PegIFN/RBV) therapy in patients infected with hepatitis C virus (HCV) genotype 1. We aimed to evaluate association of pretreatment and during treatment serum IP-10 levels with virological response to PegIFN/RBV therapy in genotype 1-infected Japanese patients with chronic hepatitis C (CHC). Methods: A total of 110 patients treated with PegIFN/RBV therapy. Serum IP-10 levels were determined by enzyme linked immunosorbent assay before therapy, after 12 weeks of treatment, and endpoint of therapy. Results: 40 (36.4%) patients obtained SVR and 72 (63.6%) resulted in non-responder (NR). From univariate analysis, age (51.8 vs. 57.8: P = 0.004); IFN treatment (First/Re-treatment) (30/10 vs. 33/37: P = 0.005); Stage (F0–2 vs. F3–4) (29/11 vs. 34/36: P = 0.015); Total volume of PegIFN (3194.8 vs 2494.4: P = 0.005); Total volume of RBV (192.4 vs.161.3: P = 0.004); HCV-RNA levels (1615.7 vs. 2110.0: P = 0.046); AST level (60.1 vs.80.4: P = 0.005); PLT level (17.8 vs.16.5: P = 0.021); g-GTP level (44.2 vs.72.9: P < 0.001); AFP level (6.4 vs. 24.2: P < 0.001); treatment period (weeks) (46.4 vs. 40.1: P = 0.005); pretreatment IP-10 levels (448.9 vs. 590.1: P = 0.008); after 12 weeks of treatment IP-10 levels (243.1 vs. 328.4: P = 0.033); endpoint of therapy IP-10 levels (280.7 vs. 374.8: P = 0.047); Rapid virological response (RVR) (12/28 vs. 1/69: P < 0.001); Early virological response (EVR) (36/4 vs. 14/56: P < 0.001); wild type at amino acid 70 in the HCV core region (30/10 vs. 33/37: P = 0.005). By multivariate analysis, Age (odds ratio (OR) 9.19 (95% confidence interval (CI) 1.52–55.72; P = 0.016), treatment period (OR 153.54 (95% CI 3.44–6860.09; P = 0.009), early virological response (EVR) (OR 126.32 (95% CI 7.87-.2026.60; P < 0.001) and after 12 weeks of treatment (OR 16.14 (95% CI 1.29-.202.13; P = 0.031) were identified as predictive factor of SVR. Conclusions: Our data suggest that pretreatment and after 12 weeks of treatment serum IP-10 levels predict SVR to PegIFN/RBV therapy in CHC genotype 1 infected patients. 259 ANTIVIRAL EFFICACY OF RIBAVIRIN MONOTHERAPY FOLLOWED BY STANDARD COMBINATION TREATMENT IN CHRONIC HEPATITIS C B. Ful ¨ op ¨ 1 , U. Mihm2 , B. Schlosser1 , M. Biermer1 , A. Brodzinski1 , 1 F. van Bommel ¨ , P. Rhode3 , P. Buggisch4 , C. Sarrazin5 , T. Berg1 . 1 Hepatology and Gastroenterology, Charite Virchow Clinic, Berlin, 2 Gastroenterology and Hepatology, Johann Wolfgang Goethe University Medical Center, Frankfurt/Main, 3 Gastroenterology and Hepatology, St Marien Hospital Hamm, Hamm, 4 Hepatology, IFI, Institute for Interdisciplinary Medicine at Asclepios Clinic St. Georg, Hamburg, 5 Gastroenterology and Hepatology, Johann Wolfgang Goethe University Medical Center, Berlin, Germany E-mail: [email protected] Ribavirin is a weak inhibitor of the hepatitis C virus NS5B RNA polymerase in vitro and probably also in vivo. After multiple dosing, steady state is achieved not until weeks 4 with a final half-life of 12 days. High initial ribavirin concentrations have been shown to be associated with successful treatment outcome. The aim of the present study was to evaluate the effect of a pretreatment with ribavirin priming followed by standard combination therapy on the initial decline of hepatitis C viremia. 89 patients from 4 centers were retrospectively analysed (54.2% male, HCV type 1 in 76.4%; treatment-naïve (n = 43), prior relapse (n = 27), prior non-response (n = 17). All patients received a ribavirin monotherapy with a starting dose of 15.2 mg/gk for an average duration of 39 days. The average log decline in HCV RNA levels during ribavirin monotherapy was 0.48 log10 (range +1.07 to −1.76; 95% CI; p < 0.001).
Patients with previous relapse showed highest response rates (mean 0.6 log10 decline) as compared to treatment naïve (0.5 log10 ) or non-responder patients (0.28 log10 ). So far, 27 out of 44 of the pretreated patients became HCV RNA undetectable after ribavirin monotherapy induction as compared to 18 in the previous treatment. Furthermore, an acceleration of the viral decline could be demonstrated in 6 nonresponder patients in whom HCV RNA levels were followed closely during the first and second treatment course (the log decline at week 4, 12 and 24 was 1.5, 2.2, and 3.6 in the previous therapy and 2.7, 4.6 and 6.3 after ribavirin pretreatment. 26 pretreated patients had a follow-up evaluation ≥6 months after stopping treatment, and 14 (2 prior nonresponse, 12 prior relapse) out of them achieved a sustained virologic response. Ribavirin monotherapy induces a mild but significant decline in hepatitis C viremia and, after adding peginterferon-alfa, also seems to accelerate the initial virologic dynamics during the following combination therapy. 260 SUCCESSFUL THERAPY WITH PEGYLATED INTERFERON ALFA-2A AND RIBAVIRIN CAUSES A SUSTAINED DECREASE IN PORTAL PRESSURE IN PATIENTS WITH CHRONIC HEPATITIS C-RELATED CIRRHOSIS M. Garcia-Retortillo1 , D. Rincon ´ 2 , A. Albillos3 , J. Colmenero1 , 1 4 2 R. Bataller , J.L. Calleja , R. Banares ˜ , J.G. Abraldes1 , J. Bosch1 , J.M. Sanchez-Tapias1 , X. Forns1 , J.C. Garcia-Pagan ´ 1 , CIBERehd Spain. 1 2 Liver Unit, Hospital Cl´ınic, Barcelona, Hospital Gregorio Mara˜ no ´n, 3 Hospital Ram´ on y Cajal, 4 Hospital Puerta de Hierro, Madrid, Spain E-mail: [email protected] Introduction: In patients with compensated hepatitis C-related cirrhosis (HC-Cirrhosis), an hepatic venous pressure gradient (HVPG) ≥10 mmHg (Clinically Significant Portal Hypertension, CSPHT) is associated with higher risk of hepatic decompensation and worse prognosis. In this setting, reduction of HVPG >10% of baseline has been shown to prevent complications from portal hypertension. Antiviral therapy is indicated in these patients, and preliminary data suggest a beneficial effect of antiviral therapy on HVPG. Aim: To assess, in patients with HC-Cirrhosis and CSPHT, the short and long-term effect of antiviral therapy with PegInterferon alfa2a (180ug weekly) and ribavirin (800–1200 mg/d) (Peg+Riba) on HVPG. Methods: In 30 patients with HC-cirrhosis and CSPH receiving antiviral therapy with Peg+Riba, HVPG was determined at baseline and after 12 weeks of therapy. In 15/17 patients with early virological response (EVR: decrease >2 logs of viral load at week 12) HVPG was again measured 6 weeks after completing 48 weeks of treatment (9 of them with SVR, and 6 without). In 5/13 patients without EVR, Peg+Riba was stopped and HVPG was again measured after a similar observational follow up period. Results: 80% of patients were male and the median age was 52±9 years. Genotype 1 represented 87% of all cases and median baseline viral load was log10 6.08±0.66. At week 12, HVPG significantly decreased from 15.5±3.8 to 13.9±3.3 mmHg (p < 0.001) with a median decrease of 9.1±13%. In 13 patients, this reduction was >10% or below the 10 mmHg threshold (HVPG responders). HVPG responders were those with higher baseline viral load (6.5±0.3 vs 5.7±0.7; p = 0.001) and those that had had a greater reduction in viral load and ALT at week 12 (−4.2±2.2 vs −2.6±2: p = 0.03 and −102±74 vs −49±71 IU/L; p = 0.06 respectively in HVPG nonresponders). In the 9 patients with SVR, the reduction in HVPG achieved at week 12 was maintained six weeks after completing antiviral therapy (12.9±2.8 mmHg (12weeks) to 12.2±3.5;p = 0.2) while HVPG tended to increase in the 11 pts without SVR or EVR (from 13.4±3.3 to 15.0±4.4 mmHg; p = 0.06).
Journal of Hepatology 2010 vol. 52 | S59–S182
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Patients with previous relapse showed highest response rates (mean 0.6 log10 decline) as compared to treatment naïve (0.5 log10 ) or non-responder patients (0.28 log10 ). So far, 27 out of 44 of the pretreated patients became HCV RNA undetectable after ribavirin monotherapy induction as compared to 18 in the previous treatment. Furthermore, an acceleration of the viral decline could be demonstrated in 6 nonresponder patients in whom HCV RNA levels were followed closely during the first and second treatment course (the log decline at week 4, 12 and 24 was 1.5, 2.2, and 3.6 in the previous therapy and 2.7, 4.6 and 6.3 after ribavirin pretreatment. 26 pretreated patients had a follow-up evaluation ≥6 months after stopping treatment, and 14 (2 prior nonresponse, 12 prior relapse) out of them achieved a sustained virologic response. Ribavirin monotherapy induces a mild but significant decline in hepatitis C viremia and, after adding peginterferon-alfa, also seems to accelerate the initial virologic dynamics during the following combination therapy. 260 SUCCESSFUL THERAPY WITH PEGYLATED INTERFERON ALFA-2A AND RIBAVIRIN CAUSES A SUSTAINED DECREASE IN PORTAL PRESSURE IN PATIENTS WITH CHRONIC HEPATITIS C-RELATED CIRRHOSIS M. Garcia-Retortillo1 , D. Rincon ´ 2 , A. Albillos3 , J. Colmenero1 , 1 4 2 R. Bataller , J.L. Calleja , R. Banares ˜ , J.G. Abraldes1 , J. Bosch1 , J.M. Sanchez-Tapias1 , X. Forns1 , J.C. Garcia-Pagan ´ 1 , CIBERehd Spain. 1 2 Liver Unit, Hospital Cl´ınic, Barcelona, Hospital Gregorio Mara˜ no ´n, 3 Hospital Ram´ on y Cajal, 4 Hospital Puerta de Hierro, Madrid, Spain E-mail: [email protected] Introduction: In patients with compensated hepatitis C-related cirrhosis (HC-Cirrhosis), an hepatic venous pressure gradient (HVPG) ≥10 mmHg (Clinically Significant Portal Hypertension, CSPHT) is associated with higher risk of hepatic decompensation and worse prognosis. In this setting, reduction of HVPG >10% of baseline has been shown to prevent complications from portal hypertension. Antiviral therapy is indicated in these patients, and preliminary data suggest a beneficial effect of antiviral therapy on HVPG. Aim: To assess, in patients with HC-Cirrhosis and CSPHT, the short and long-term effect of antiviral therapy with PegInterferon alfa2a (180ug weekly) and ribavirin (800–1200 mg/d) (Peg+Riba) on HVPG. Methods: In 30 patients with HC-cirrhosis and CSPH receiving antiviral therapy with Peg+Riba, HVPG was determined at baseline and after 12 weeks of therapy. In 15/17 patients with early virological response (EVR: decrease >2 logs of viral load at week 12) HVPG was again measured 6 weeks after completing 48 weeks of treatment (9 of them with SVR, and 6 without). In 5/13 patients without EVR, Peg+Riba was stopped and HVPG was again measured after a similar observational follow up period. Results: 80% of patients were male and the median age was 52±9 years. Genotype 1 represented 87% of all cases and median baseline viral load was log10 6.08±0.66. At week 12, HVPG significantly decreased from 15.5±3.8 to 13.9±3.3 mmHg (p < 0.001) with a median decrease of 9.1±13%. In 13 patients, this reduction was >10% or below the 10 mmHg threshold (HVPG responders). HVPG responders were those with higher baseline viral load (6.5±0.3 vs 5.7±0.7; p = 0.001) and those that had had a greater reduction in viral load and ALT at week 12 (−4.2±2.2 vs −2.6±2: p = 0.03 and −102±74 vs −49±71 IU/L; p = 0.06 respectively in HVPG nonresponders). In the 9 patients with SVR, the reduction in HVPG achieved at week 12 was maintained six weeks after completing antiviral therapy (12.9±2.8 mmHg (12weeks) to 12.2±3.5;p = 0.2) while HVPG tended to increase in the 11 pts without SVR or EVR (from 13.4±3.3 to 15.0±4.4 mmHg; p = 0.06).
Journal of Hepatology 2010 vol. 52 | S59–S182
S109