- Email: [email protected]
52 INCREASED MORTALITY ON THE LIVER TRANSPLANT WAITING LIST IN FEMALES UNDER THE MELD ALLOCATION SYSTEM: UTILITY OF REVISED MELD INCORPORATING ESTIMATED GLOMERULAR FILTRATION RATE
ORAL PRESENTATIONS 50 PREGNANCY RESOLVES LIVER FIBROSIS AND IMPROVES SCLEROSING CHOLANGITIS IN MDR2 (ABCB4) −/− MICE VIA DIRECT ANTI-INFLAMMATORY EFFECTS OF SEX HORMONES E. Halilbasic, T. Claudel, J. Gumhold, S. Halsegger, D. Silbert, P. Fickert, M. Trauner. Laboratory of Experimental and Molecular Hepatology, Divison of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria E-mail: [email protected] Background and Aims: Liver fibrosis in chronic hepatitis C progresses with menopause while postmenopausal women with hormone replacement therapy have lower degrees of liver fibrosis. Moreover, estrogen treatment leads to improvement of liver injury in CCl4-induced liver fibrosis in rats. On the other hand, mutations in MDR3 (ABCB4) gene are associated with increased risk for intrahepatic cholestasis in pregnancy (ICP). The pathogenesis of ICP may be linked to the effects of estrogen and progesterone metabolites on bile secretion. Therefore, we aimed to test the effects of pregnancy on development of liver fibrosis and cholangitis in Mdr2−/− mice, known to develop liver injury due to abnormal biliary composition. Methods: Pregnant (18.5 days) Mdr2−/− mice were compared with age-matched Mdr2−/− and wild-type control. Liver injury was evaluated using serum liver enzymes and liver histology. Markers of hepatic fibrosis, ductular proliferation and inflammation were studied using Q-PCR and Western blotting. Bile flow and biliary composition were determined. Anti-inflammatory effects of estrogen and progesterone were studied in vitro in female mouse macrophage cell line (RAW264) and bile duct epithelial cell line (BEC) upon activation with LPS and TNF-a respectively. Results: Pregnancy led to reduction of ALT, AP and bile acid levels in Mdr2−/− mice and improved liver histology. Moreover, reduction of liver fibrosis correlated with decreased hydroxyproline content, mRNA expression of Tgf-1b, Col1a1, Col1a2 and protein expression of a-SMA in pregnant Mdr2−/− mice. In addition, hepatic inflammatory response was lowered during pregnancy resulting in down-regulation of Tnf-a, Il-6, Mcp-1 mRNA. No changes in biliary bile acid, cholesterol or phospholipid content were observed between pregnant and non-pregnant mice. Estrogen and progesterone directly reduced Tnf-a, Mcp-1 and iNos production in LPS and Tnf-a treated RAW264 and BEC cells. Conclusions: Pregnancy ameliorates liver injury in Mdr2−/− mice without having striking effects on bile acid homeostasis. Direct antiinflammatory and anti-fibrotic effects of estrogen and progesterone on hepatic inflammatory cells and reactive cholangiocytes may explain the unexpected improvement of sclerosing cholangitis and cholestatic liver injury in Mdr2−/− mice. 51 THE SAFETY AND EFFICACY OF HIGH-DOSE PROTON BEAM RADIOTHERAPY FOR HEPATOCELLULAR CARCINOMA; A PHASE II PROSPECTIVE TRIAL D. Bush1 , J. Slater1 , Z. Kayali2 . 1 Loma Linda University Medical Center, 2 Liver Transplant Program, Loma Linda University Medical Center, Loma Linda, CA, USA E-mail: [email protected] Background and Aims: Proton Beam Therapy (PBT) may provide useful local-regional treatment for hepatocellular carcinoma (HCC). The goal of this study is to evaluate the safety and efficacy of PBT as a treatment for HCC. Methods: This is a Phase II prospective trial. Included patients were cirrhotics with HCC. Diagnosis of HCC was based on radiological features and/or biopsy. Non-cirrhotic patients, resectable HCC, prior loco regional treatment, >3 lesions, and those with extrahepatic metastasis were excluded. Patients received 63 cobalt Gy equivalent (CGE) delivered over a 3-week period with PBT. S24
Results: Seventy-six patients were treated. The mean age was 63 years, mean tumor size 5.5 cm, 24% had Child class C cirrhosis, 16% had MELD score of >15, and 54% were outside the Milan criteria. Acute toxicity was minimal and all patients were able to complete the full course of treatment. No patient had any significant radiation induced liver disease (RILD) or significant elevation in MELD score within 6 months following treatment. The median progression-free survival (PFS) for the entire group was 36 months. Progression free survival for patients within Milan criteria was significantly higher compared to patients outside Milan (Figure) (p = 0.01 log rank).
Progression-free survival. The 3-year PFS for patients within Milan was 60%. The median PFS for patients outside Milan was 19 months. Eighteen patients were eligible and underwent liver transplantation with 6 (33%) explants showing no residual tumor, and 7 (39%) showing only microscopic residual. Conclusion: Proton Beam Radiotherapy is safe and effective local-regional therapy for hepatocellular carcinoma. Randomized controlled trials to compare its efficacy to other therapies are warranted. 52 INCREASED MORTALITY ON THE LIVER TRANSPLANT WAITING LIST IN FEMALES UNDER THE MELD ALLOCATION SYSTEM: UTILITY OF REVISED MELD INCORPORATING ESTIMATED GLOMERULAR FILTRATION RATE R.P. Myers1 , A.A.M. Shaheen1 , A.I. Aspinall1 , R.R. Quinn2 , K.W. Burak1 . 1 Liver Unit, 2 Division of Nephrology, University of Calgary, Calgary, AB, Canada E-mail: [email protected] Background and Aims: Women may be disadvantaged under the Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) due to its reliance on serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess the utility of a revised MELD including estimated glomerular filtration rate (eGFR) for the prediction of waiting list mortality. Methods: Adults registered on the LT waiting list in the United States between 03/2002 and 12/2007 were identified using the UNOS STAR database. We compared components of MELD, eGFR according to the MDRD equation, and the probability of LT and death within 3 months of registration between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for predicting 3-month mortality were compared using c-statistics. Results: In total, 30,032 patients (36% female) met the inclusion criteria; 7% died and 20% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dL), eGFR (72 vs. 83 mL/min/1.73 m2 ), and MELD (14 vs. 15; P < 0.0005 for all comparisons), but within most MELD strata, had higher serum bilirubin and INR values. After adjusting
Journal of Hepatology 2010 vol. 52 | S23–S41
ORAL PRESENTATIONS for relevant covariates including serum creatinine, women were less likely than men to receive a LT (hazard ratio [HR] 0.83; 95% CI 0.79– 0.98) and had greater 3-month mortality (HR 1.13; 95% CI 1.04– 1.24). Revision of MELD and MELDNa with eGFR instead of serum creatinine did not improve prediction of 3-month mortality (cstatistics: MELD 0.899, MELD-eGFR 0.897, MELDNa 0.912, MELDNaeGFR 0.907). Conclusions: Women are disadvantaged under the MELD allocation system perhaps due to a systematic bias related to the inclusion of serum creatinine. Since revision of MELD with eGFR does not improve discrimination for mortality, additional studies aimed at refining MELD should consider direct measures of renal function.
Parallel Session 6: HEPATITIS C: CLINICAL ADVANCES AND THERAPY
53 RELATION BETWEEN SUSTAINED VIROLOGIC RESPONSE AND INSULIN RESISTANCE IN PATIENTS WITH GENOTYPE 1 OR 2/3 CHRONIC HEPATITIS C A. Thompson1 , M. Diago2 , G. Foster3 , P. Ferenci4 , Y. Lurie5 , 8 C. Stanciu6 , M. Jablkowski7 , D. Haussinger ¨ , P. Urbanek9 , S. Pianko10 , W.-L. Chuang11 , G. Subramanian12 , J. McHutchison13 , for the ACHIEVE Study Group. 1 GI/Hepatology Research Program, Duke Clinical Research Institute, Durham, NC, USA; 2 Hospital Quiron de Valencia, Valencia, Spain; 3 Barts and The London School of Medicine, London, UK; 4 Medical University of Vienna, Vienna, Austria; 5 Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; 6 Institute de Gastroenterologie si Hepatologie, Iasi, Romania; 7 Medical University of Lodz, Lodz, Poland; 8 Heinrich Heine University, D¨ usseldorf, Germany; 9 Intern Klinika UVN Praha, Prague, Czech Republic; 10 Monash Medical Centre, Clayton, VIC, Australia; 11 Kaohsiung Medical University, Kaohsiung, Taiwan R.O.C.; 12 Human Genome Sciences, Inc., Rockville, MD, 13 Duke Clinical Research Institute, Durham, NC, USA E-mail: [email protected] Background and Aims: Chronic hepatitis C (CHC) has been associated with an increased prevalence of diabetes and insulin resistance (IR). Recently, a genotype-specific association between HCV genotype 1 and IR has been proposed. It remains unclear, however, whether this is a causal relationship. The present study investigated the association of sustained virologic response (SVR) with IR in patients enrolled in the ACHIEVE 1 and 2/3 trials. Methods: 2255 treatment-naïve patients with genotype 1 or 2/3 CHC were enrolled in 2 separate phase 3, active-controlled studies of albinterferon alfa-2b vs peginterferon alfa-2a plus ribavirin for 48 or 24 weeks, respectively. IR was measured at wk 0, 12, 24, or 48, and post-treatment wk12 using the homeostasis model for assessment of IR (HOMA-IR). Clinical evaluation by a single pathologist included age, gender, race, BMI, HCV viral load, alanine aminotransferase, g-glutamyl transpeptidase, total cholesterol, triglycerides, and baseline liver biopsy for steatosis, METAVIR inflammatory grade, and fibrosis stage. IR was considered categorically, setting a threshold of HOMA-IR >3. Change in HOMAIR post-therapy was considered as a continuous variable; HOMA-IR data were log-transformed for analysis as a continuous variable. The ACHIEVE 1 and 2/3 cohorts were analyzed separately. Results: Matched pre- and 12wk post HOMA-IR measurements were available from 1038 nondiabetic patients (genotype 1 = 497, genotype 2/3 = 541). Respective SVR rates were 60% and 84% in genotype 1 and 2/3 patients. Baseline mean HOMA-IR scores were higher in patients with genotype 1 than with 2/3 (3.4 vs 2.9;
P=.006). SVR was associated with a reduction in prevalence of IR (P < 0.001) and in mean HOMA-IR (P = 0.004) in genotype 1 patients, but not in genotype 2/3. This was independent of changes in BMI, alanine aminotransferase, g-glutamyl transpeptidase, and lipid levels. HOMA-IR did not change in nonresponders. No association between SVR and IR was seen when genotype 2 or 3 patients were considered separately. Conclusions: SVR was associated with a reduction in HOMAIR in patients with genotype 1 CHC, but not genotype 2/3. The results suggest that HCV genotype 1 can play a causal role in the development of IR, which may be reversed by viral eradication. 54 COMPLETELY INDIVIDUALIZED TREATMENT DURATIONS (24, 30, 36, 42, 48, 60 OR 72 WEEKS) WITH PEGINTERFERON-ALFA-2B AND RIBAVIRIN IN HCV GENOTYPE 1-INFECTED PATIENTS (INDIV-2 STUDY) 3 C. Sarrazin1 , S. Schwendy2 , B. Moller ¨ , N. Dikopoulos4 , P. Buggisch5 , J. Encke6 , G. Teuber7 , T. Goeser8 , R. Thimme9 , H. Klinker10 , W.O. Boecher11 , E. Schulte-Frohlinde12 , R. Prinzing13 , T. Berg14 , S. Zeuzem1 . 1 Medizinische Klinik 1, J. W. Goethe-University Hospital, Frankfurt/Main, 2 University Hospital Munich, Munich, 3 Leberzentrum Checkpoint, Berlin, 4 University Hospital Ulm, Ulm, 5 Institut f¨ ur Interdisziplin¨ are Medizin, Hamburg, 6 Johanna Etienne Krankenhaus, Neuss, 7 Imterdisziplin¨ ares Facharztzentrum, Frankfurt/Main, 8 University Hospital Cologne, Cologne, 9 University Hospital Freiburg, Freiburg im Breisgau, 10 University Hospital W¨ urzburg, W¨ urzburg, 11 University Hospital Mainz, Mainz, 12 Klinikum Freising, Freising, 13 Essex Pharma, Munich, 14 University Hospital Leipzig, Leipzig, Germany E-mail: [email protected]
Introduction: Shortening of treatment with peginterferon and ribavirin to 24-weeks in patients with chronic hepatitis-C genotype-1, low baseline viral load and rapid-virologic-response (RVR) is approved in Europe. It is unknown whether complete individualized treatment durations according to baseline viral load and initial viral decline are possible. Methods: 398 treatment-naïve HCV genotype-1 patients were enrolled in a multicenter, randomized trial with peginterferonalfa-2b and ribavirin. Patients received individualized treatment durations for 24, 30, 36, 42, 48, 60 or 72 weeks according to low or high baseline viral load (LVL/HVL, cut-off 800.000IU/ml) and undetectable HCV-RNA at week 4, 6, 8, 12 and 24 by a highly sensitive assay (TMA). Sustained virologic response (SVR) rates were compared to 224 patients treated for 48 weeks. Sustained virologic response (SVR) based on ITT INDIV-2
neg. neg. neg. neg. neg. neg. neg. neg. neg.
wk. 4 (RVR) + LVL wk. 4 (RVR) + HVL wk. 6 + LVL wk. 6 + HVL wk. 8 + LVL wk. 8 + HVL wk. 12 + LVL wk. 12 + HVL wk 24 + LVL
Control
Treatment duration (n = 398)
SVR
Treatment duration (n = 224)
SVR
24 30 30 36 42 48 48 60 60
88% 86% 91% 85% 72% 82% 82% 56% 56%
48 48 48 48 48 48 48 48 48
93% 100% 77% 78% 100% 88% 88% 42% 42%
weeks weeks weeks weeks weeks weeks weeks weeks weeks
(n = 41) (n = 7) (n = 23) (n = 13) (n = 29) (n = 22) (n = 33) (n = 39) (n = 43)
weeks weeks weeks weeks weeks weeks weeks weeks weeks
(n = 30) (n = 3) (n = 18) (n = 13) (n = 8) (n = 8) (n = 16) (n = 24) (n = 19)
Results: Overall SVR rates were similar in patients treated with individualized durations and the control group (53% vs. 48%). SVR rates of groups with individualized treatment durations and patients with HCV-RNA negativity after identical treatment durations but 48 weeks treatment were not statistically different. Patients with HVL and LVL and first time HCV-RNA negativity at week 24 and 30, respectively were treated for 72 weeks and achieved 50% SVR rates. The remaining patients are shown in the table.
Journal of Hepatology 2010 vol. 52 | S23–S41
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Results: Seventy-six patients were treated. The mean age was 63 years, mean tumor size 5.5 cm, 24% had Child class C cirrhosis, 16% had MELD score of >15, and 54% were outside the Milan criteria. Acute toxicity was minimal and all patients were able to complete the full course of treatment. No patient had any significant radiation induced liver disease (RILD) or significant elevation in MELD score within 6 months following treatment. The median progression-free survival (PFS) for the entire group was 36 months. Progression free survival for patients within Milan criteria was significantly higher compared to patients outside Milan (Figure) (p = 0.01 log rank).
Progression-free survival. The 3-year PFS for patients within Milan was 60%. The median PFS for patients outside Milan was 19 months. Eighteen patients were eligible and underwent liver transplantation with 6 (33%) explants showing no residual tumor, and 7 (39%) showing only microscopic residual. Conclusion: Proton Beam Radiotherapy is safe and effective local-regional therapy for hepatocellular carcinoma. Randomized controlled trials to compare its efficacy to other therapies are warranted. 52 INCREASED MORTALITY ON THE LIVER TRANSPLANT WAITING LIST IN FEMALES UNDER THE MELD ALLOCATION SYSTEM: UTILITY OF REVISED MELD INCORPORATING ESTIMATED GLOMERULAR FILTRATION RATE R.P. Myers1 , A.A.M. Shaheen1 , A.I. Aspinall1 , R.R. Quinn2 , K.W. Burak1 . 1 Liver Unit, 2 Division of Nephrology, University of Calgary, Calgary, AB, Canada E-mail: [email protected] Background and Aims: Women may be disadvantaged under the Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) due to its reliance on serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess the utility of a revised MELD including estimated glomerular filtration rate (eGFR) for the prediction of waiting list mortality. Methods: Adults registered on the LT waiting list in the United States between 03/2002 and 12/2007 were identified using the UNOS STAR database. We compared components of MELD, eGFR according to the MDRD equation, and the probability of LT and death within 3 months of registration between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for predicting 3-month mortality were compared using c-statistics. Results: In total, 30,032 patients (36% female) met the inclusion criteria; 7% died and 20% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dL), eGFR (72 vs. 83 mL/min/1.73 m2 ), and MELD (14 vs. 15; P < 0.0005 for all comparisons), but within most MELD strata, had higher serum bilirubin and INR values. After adjusting
Journal of Hepatology 2010 vol. 52 | S23–S41
ORAL PRESENTATIONS for relevant covariates including serum creatinine, women were less likely than men to receive a LT (hazard ratio [HR] 0.83; 95% CI 0.79– 0.98) and had greater 3-month mortality (HR 1.13; 95% CI 1.04– 1.24). Revision of MELD and MELDNa with eGFR instead of serum creatinine did not improve prediction of 3-month mortality (cstatistics: MELD 0.899, MELD-eGFR 0.897, MELDNa 0.912, MELDNaeGFR 0.907). Conclusions: Women are disadvantaged under the MELD allocation system perhaps due to a systematic bias related to the inclusion of serum creatinine. Since revision of MELD with eGFR does not improve discrimination for mortality, additional studies aimed at refining MELD should consider direct measures of renal function.
Parallel Session 6: HEPATITIS C: CLINICAL ADVANCES AND THERAPY
53 RELATION BETWEEN SUSTAINED VIROLOGIC RESPONSE AND INSULIN RESISTANCE IN PATIENTS WITH GENOTYPE 1 OR 2/3 CHRONIC HEPATITIS C A. Thompson1 , M. Diago2 , G. Foster3 , P. Ferenci4 , Y. Lurie5 , 8 C. Stanciu6 , M. Jablkowski7 , D. Haussinger ¨ , P. Urbanek9 , S. Pianko10 , W.-L. Chuang11 , G. Subramanian12 , J. McHutchison13 , for the ACHIEVE Study Group. 1 GI/Hepatology Research Program, Duke Clinical Research Institute, Durham, NC, USA; 2 Hospital Quiron de Valencia, Valencia, Spain; 3 Barts and The London School of Medicine, London, UK; 4 Medical University of Vienna, Vienna, Austria; 5 Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; 6 Institute de Gastroenterologie si Hepatologie, Iasi, Romania; 7 Medical University of Lodz, Lodz, Poland; 8 Heinrich Heine University, D¨ usseldorf, Germany; 9 Intern Klinika UVN Praha, Prague, Czech Republic; 10 Monash Medical Centre, Clayton, VIC, Australia; 11 Kaohsiung Medical University, Kaohsiung, Taiwan R.O.C.; 12 Human Genome Sciences, Inc., Rockville, MD, 13 Duke Clinical Research Institute, Durham, NC, USA E-mail: [email protected] Background and Aims: Chronic hepatitis C (CHC) has been associated with an increased prevalence of diabetes and insulin resistance (IR). Recently, a genotype-specific association between HCV genotype 1 and IR has been proposed. It remains unclear, however, whether this is a causal relationship. The present study investigated the association of sustained virologic response (SVR) with IR in patients enrolled in the ACHIEVE 1 and 2/3 trials. Methods: 2255 treatment-naïve patients with genotype 1 or 2/3 CHC were enrolled in 2 separate phase 3, active-controlled studies of albinterferon alfa-2b vs peginterferon alfa-2a plus ribavirin for 48 or 24 weeks, respectively. IR was measured at wk 0, 12, 24, or 48, and post-treatment wk12 using the homeostasis model for assessment of IR (HOMA-IR). Clinical evaluation by a single pathologist included age, gender, race, BMI, HCV viral load, alanine aminotransferase, g-glutamyl transpeptidase, total cholesterol, triglycerides, and baseline liver biopsy for steatosis, METAVIR inflammatory grade, and fibrosis stage. IR was considered categorically, setting a threshold of HOMA-IR >3. Change in HOMAIR post-therapy was considered as a continuous variable; HOMA-IR data were log-transformed for analysis as a continuous variable. The ACHIEVE 1 and 2/3 cohorts were analyzed separately. Results: Matched pre- and 12wk post HOMA-IR measurements were available from 1038 nondiabetic patients (genotype 1 = 497, genotype 2/3 = 541). Respective SVR rates were 60% and 84% in genotype 1 and 2/3 patients. Baseline mean HOMA-IR scores were higher in patients with genotype 1 than with 2/3 (3.4 vs 2.9;
P=.006). SVR was associated with a reduction in prevalence of IR (P < 0.001) and in mean HOMA-IR (P = 0.004) in genotype 1 patients, but not in genotype 2/3. This was independent of changes in BMI, alanine aminotransferase, g-glutamyl transpeptidase, and lipid levels. HOMA-IR did not change in nonresponders. No association between SVR and IR was seen when genotype 2 or 3 patients were considered separately. Conclusions: SVR was associated with a reduction in HOMAIR in patients with genotype 1 CHC, but not genotype 2/3. The results suggest that HCV genotype 1 can play a causal role in the development of IR, which may be reversed by viral eradication. 54 COMPLETELY INDIVIDUALIZED TREATMENT DURATIONS (24, 30, 36, 42, 48, 60 OR 72 WEEKS) WITH PEGINTERFERON-ALFA-2B AND RIBAVIRIN IN HCV GENOTYPE 1-INFECTED PATIENTS (INDIV-2 STUDY) 3 C. Sarrazin1 , S. Schwendy2 , B. Moller ¨ , N. Dikopoulos4 , P. Buggisch5 , J. Encke6 , G. Teuber7 , T. Goeser8 , R. Thimme9 , H. Klinker10 , W.O. Boecher11 , E. Schulte-Frohlinde12 , R. Prinzing13 , T. Berg14 , S. Zeuzem1 . 1 Medizinische Klinik 1, J. W. Goethe-University Hospital, Frankfurt/Main, 2 University Hospital Munich, Munich, 3 Leberzentrum Checkpoint, Berlin, 4 University Hospital Ulm, Ulm, 5 Institut f¨ ur Interdisziplin¨ are Medizin, Hamburg, 6 Johanna Etienne Krankenhaus, Neuss, 7 Imterdisziplin¨ ares Facharztzentrum, Frankfurt/Main, 8 University Hospital Cologne, Cologne, 9 University Hospital Freiburg, Freiburg im Breisgau, 10 University Hospital W¨ urzburg, W¨ urzburg, 11 University Hospital Mainz, Mainz, 12 Klinikum Freising, Freising, 13 Essex Pharma, Munich, 14 University Hospital Leipzig, Leipzig, Germany E-mail: [email protected]
Introduction: Shortening of treatment with peginterferon and ribavirin to 24-weeks in patients with chronic hepatitis-C genotype-1, low baseline viral load and rapid-virologic-response (RVR) is approved in Europe. It is unknown whether complete individualized treatment durations according to baseline viral load and initial viral decline are possible. Methods: 398 treatment-naïve HCV genotype-1 patients were enrolled in a multicenter, randomized trial with peginterferonalfa-2b and ribavirin. Patients received individualized treatment durations for 24, 30, 36, 42, 48, 60 or 72 weeks according to low or high baseline viral load (LVL/HVL, cut-off 800.000IU/ml) and undetectable HCV-RNA at week 4, 6, 8, 12 and 24 by a highly sensitive assay (TMA). Sustained virologic response (SVR) rates were compared to 224 patients treated for 48 weeks. Sustained virologic response (SVR) based on ITT INDIV-2
neg. neg. neg. neg. neg. neg. neg. neg. neg.
wk. 4 (RVR) + LVL wk. 4 (RVR) + HVL wk. 6 + LVL wk. 6 + HVL wk. 8 + LVL wk. 8 + HVL wk. 12 + LVL wk. 12 + HVL wk 24 + LVL
Control
Treatment duration (n = 398)
SVR
Treatment duration (n = 224)
SVR
24 30 30 36 42 48 48 60 60
88% 86% 91% 85% 72% 82% 82% 56% 56%
48 48 48 48 48 48 48 48 48
93% 100% 77% 78% 100% 88% 88% 42% 42%
weeks weeks weeks weeks weeks weeks weeks weeks weeks
(n = 41) (n = 7) (n = 23) (n = 13) (n = 29) (n = 22) (n = 33) (n = 39) (n = 43)
weeks weeks weeks weeks weeks weeks weeks weeks weeks
(n = 30) (n = 3) (n = 18) (n = 13) (n = 8) (n = 8) (n = 16) (n = 24) (n = 19)
Results: Overall SVR rates were similar in patients treated with individualized durations and the control group (53% vs. 48%). SVR rates of groups with individualized treatment durations and patients with HCV-RNA negativity after identical treatment durations but 48 weeks treatment were not statistically different. Patients with HVL and LVL and first time HCV-RNA negativity at week 24 and 30, respectively were treated for 72 weeks and achieved 50% SVR rates. The remaining patients are shown in the table.
Journal of Hepatology 2010 vol. 52 | S23–S41
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