Adverse Events in treatment chronic hepatitis C patients with PegInterferon and Ribavirin What would your management decision be? CASE STUDY Pham Thi Thu Thuy MD, PhD Ho Chi Minh City Vietnam
Serious Adverse Events and Adverse Events Asian Caucasian n = 86 % n = 63 % Serious Adverse Events 15 17.4% 13 20.6% -Death 0 0% 0 0% -Sepsis 0 0% 3 4.8% -Decompensation 1 1.2% 3 4.8% -Blood transfusions 16 18.6% 5 7.9% Adverse Events -Anemia (<10g/dl) 40 46.5% 38 60.3% -Neutropenia (<500 cells/dl) 1 1.2% 7 11.1% -Thrombocytopenia(<30,000/dl) 2 2.3% 5 7.9% -Skin Rashes 8 9.3% 19 30.2% -Weight loss 25 29.1% 30 47.6% -Dysgusia 21 24.4% 48 76.2% -Diarrhea 1 1.2% 5 7.9% -Nausea 9 10.5% 12 19.0% Discontinuations - Due to AEs 4 4.6% 9 14.3% - Fulfilled stopping rules 15 17.4% 12 19.0%
Case history 54 year old Vietnamese woman She lives in HCM city and works as a teacher The patient presented in December 2012 with fatigue and anorexia 48 kg (BMI: 20.5) Diagnosed with HCV in 2008 Negative for both HBV and HIV antibodies No prior HCV treatment Physical examination unremarkable Single
Family and other history Parents alive, HBV and HCV status unknown Operation for appendicitis in 2002 No alcohol, non-smoker Hypertension for 4 years Treated with Adalate LA 30mg, 1 tablet/day
Laboratory investigations HCV RNA:7.35 x 10 6 copies/ml HCV genotype 6b- IL28B: CT AST: 44 IU/L; ALT: 65 IU/L GGT: 45 IU/mL Total bilirubin: 0.8mg/100mL WBC: 6.55 x 10 9 /L; neutrophils: 61% Haematocrit: 43.6%; haemoglobin: 14.2 g/dl Platelets: 259 x 10 9 /L Thyroid stimulating hormone: 1.75 miu/l Antinuclear antibody test: negative Glycemia: 5.65 mmol/l Creatinin:0.8mg% Albumin:3.9g% Alpha-fetoprotein: 5 ng/ml FibroScan: F3 (Fs=12.7 Kpa) Abdomen US: chronic hepatitis
Treatment regimen for this patient Peginterferon alfa-2a 180 mg/week and ribavirin 800 mg/day
Week 4 follow-up Fatigue and headache 47kg HCV RNA: negative AST: 32 IU/L; ALT: 35 IU/L GGT: 37 IU/mL WBC: 3.8 10 9 /L; neutrophils: 42% Haematocrit: 31.7%; haemoglobin : 10.6 g/dl Platelets: 189 x 10 9 /L Thyroid stimulating hormone: 2.15 miu/l
Week 8 follow-up Fatigue 44kg Insomnia (from 1am to 4 am) AST: 28 IU/L; ALT: 30 IU/L WBC: 3.4 10 9 /L; neutrophils: 41% Haematocrit: 30.1%; haemoglobin : 10.2 g/dl Platelets: 135 x 10 9 /L Thyroid stimulating hormone: 1.56 miu/l
What would your management decision be now? 1 Work with the psychologist 2 Medicines 3 Doing exercise
Week 12: follow-up Fatigue, myalgia HCV RNA: negative Weight: 42 kg AST: 26 IU/L; ALT: 28 IU/L GGT:32 IU/ml WBC:3.2 x 10 9 /L; neutrophils: 38% Haematocrit: 28.4%; haemoglobin: 8.9 g/dl Platelets: 115 x 10 9 /L Thyroid stimulating hormone: 1.48 miu/l
What would your management decision MEDIC CENTER be now? 1 Reduce peginterferon dose 2 Reduce ribavirin dose 3 continue treatment, plus Erythropoietin and control Hb level
% of Patients ( 95 % CL ) MEDIC CENTER Primary Efficacy Results* 100 80 82 82 71 71 RBV DR EPO 60 40 20 203 249 205 251 EOT Response 178 249 SVR 10 178 251 19 196 10 19 197 Relapse *Presented at EASL, 2012
Week 16: follow-up Chest pain Cardioechography: ischemic heart disease Weight: 39 kg WBC: 2.9 x 10 9 /L; neutrophils: 36% Haematocrit: 25.7%; haemoglobin: 8.3 g/dl Platelets: 103 x 10 9 /L Thyroid stimulating hormone: 3.6 miu/l
What would your management decision MEDIC CENTER be now? 1 Reduce peginterferon and/or ribavirin dose 2 Stop treatment until heart disease is well-controlled 3 Work with the cardiologist and continue treatment
Treatment decision Continue with current HCV treatment regimen plus erythropoietin and medication for heart disease
FibroScan: F2 (Fs=8.6 Kpa) MEDIC CENTER Week 24: follow-up Patient feels well HCV RNA: negative AST: 24 IU/L; ALT: 26 IU/L GGT:35 IU/mL Creatinin:0.8mg% WBC: 3.2 10 9 /L; N: 45% Hct: 26.5%; Hb: 8.9 g/dl Platelets: 96 10 9 /L TSH: 1.17 miu/l Abdomen US: normal
What would be your next treatment MEDIC CENTER decision for this patient? 1 Stop treatment at 24 weeks 2 Continue treatment until 48 weeks
Virolgoic response rate (%) MEDIC CENTER Similar SVR rates with 24 or 48 weeks treatment in HCV genotype 6 patients in Vietnam 48 weeks Peg-IFN ɑ-2a 180 g/wk plus RBV 15 mg/kg/day 24 weeks Peg-IFN ɑ-2a 180 g/wk plus RBV 15 mg/kg/day 100 80 60 P>0.05 -P>0.05- P>0.05 92.06 93.10 80.95 84.12 79.31 79.3 P>0.05 79.36 72.41 40 20 0 RVR cevr ETR SVR Thu Thuy, Hepatology, May 2012 V56
Rapid virological response is a good predictor of SVR Yes n=51 (80.95%) SVR 49/51 (96.07%) Group I n=63 Week 4 RVR? No n=12 (19.05%) SVR 1/12 (8.33%) Yes n=23 (79.31%) SVR 21/23 (91.3%) Group II n=29 Week 4 RVR? No n=6 (20.69%) SVR 0/6 (0%) Thu Thuy, Hepatology May 2012, V 56
SVR rate (%) MEDIC CENTER RVR may be predictive of achieving an SVR in genotype 6 patients Peg-IFN α-2a 180 µg/week plus weight-based RBV 800 1200 mg/day 100 80 82 83 24 weeks 48 weeks 60 40 20 33 29 0 n= 17 12 3 7 Patients with RVR Patients without RVR Lam KD et al. Hepatology 2010; 52: 1573 1580
24 weeks after stopping treatment Patient feels well Weight: 44 kg HCV RNA: negative AST: 22 IU/L; ALT: 26 IU/L WBC: 4.34 10 9 /L Hct: 36.3% Hb: 12.2 g/dl Platelets: 258 10 9 /L TSH: 1.45 miu/l Abdomen US: normal FibroScan: F1 (Fs=6.7 Kpa)