Case 2
Case history 57 year old Vietnamese man He lives in HCM city and works as a engineer The patient presented in July 2012 with fatigue Diagnosed with HCV in 2004 Negative for both HBV and HIV antibodies Treatment with Pegintron + Ribavirin for 48 Weeks- relapse. (2007) Physical examination unremarkable 71 kg (BMI: 24.85)
Family and other history No HBV, HCV infection in his family No operation or blood transfusion in the past Non-smoker, drink alcohol but stop 10 years ago
Laboratory investigations HCV RNA: 1.2 E+7 IU/mL HCV genotype 1b IL28B=CC AST: 95 IU/L; ALT: 54 IU/L; GGT: 82 IU/L Total bilirubin: 0.9mg/100mL WBC: 5.4 x 10 9 /L; neutrophils: 56% Haematocrit: 44.6%; haemoglobin: 15.2 g/dl Platelets: 135 x 10 9 /L Thyroid stimulating hormone: 1.41 miu/l Antinuclear antibody test: negative Glycemia: 5.35 mmol/l Albumin:3.10g/mL Creatinin:0.9mg% Alpha-fetoprotein: 8.2 ng/ml FibroScan: F4 (Fs= 32 kpa) Abdomen US: chronic hepatitis ECG: Normal
What management decision would you make at this time? 1. Initiate treatment with Peginterferon and Ribavirin for 48 w 2. Initiate treatment with Peginterferon and Ribavirin for 72 w 3. Wait for new therapy DAA
Treatment regimen for this patient Peginterferon alfa-2a 180 mcg/week and ribavirin 1000 mg/day
Week 4 follow-up Fatigue and anorexia 69 kg HCV RNA: 1.24 E+5 IU/mL AST: 97 IU/L; ALT: 59 IU/L; GGT: 86 IU/L AFP: 6 ng/ml WBC: 4.51 10 9 /L; neutrophils: 39%, Eos: 1% Haematocrit: 39.8%; haemoglobin : 11.5 g/dl Platelets: 125 x 10 9 /L, Albumin: 3.2g/100mL Thyroid stimulating hormone: 1.9 miu/l
Fail RVR = poor SVR rates HCV genotype 1: Treatment naïve Treatment failures Cirrhosis PR Lead-in 4 weeks RVR (+) RVR (-) >86% SVR 34%-41.7% SVR Options available Continue PR 48w Extend PR to 72w Add boceprevir Stop therapy and wait for new second generation DAA McHutchison et al, NEJM 2009;361:580-93 Katz et al, Cochrane Database Systematic Rev 2012;9:CD008516 Liu CH et al, Antiviral Therapy 2012;17:477-84
SVR (%) MEDIC CENTER IL28B rs 192789860 Polymorphisms and Response to PegIFN/RBV by HCV Genotype Genotype 1 Genotype 2/3 Genotype 4 100 80 60 40 79 81 44 41 77 63 85 49 23 CC CT TT 20 0 Albert Friedrich Stättermayer et al., Clinical Gastroenterology and Hepatology Volume 9, Issue 4, Pages 344-350., April 2011
Week 12 follow-up Anorexia HCV RNA: 1.08 E+3 IU/mL AST: 88 IU/L; ALT: 69 IU/L; GGT: 96 IU/L WBC: 3.9 10 9 /L; neutrophils: 42%, Eos:2% Haematocrit: 33.8%; haemoglobin : 11.2 g/dl Platelets: 104 x 10 9 /L; Albumin:3.2 g/100ml Thyroid stimulating hormone: 0.8 miu/l AFP: 9 ng/ml Bilirubin-T: 0.8mg% Creatinin: 0.9mg% Ferritin: 2100 ng/ml US:Chronic hepatitis
What would your management decision be now? 1. Stop treatment 2. Continue treatment
% SVR MEDIC CENTER SVR of Patients with Late HCV RNA-Negativity 78 54.54 38 29 6.66 18 17 9 Medic Brian Thomas Berg Tatsuya 72 weeks of treatment 48 weeks of treatment Thu Thuy, VN Hepatology, 2010 Brian, Hepatology, 2007 Thomas Berg, Gastroenterology, 2006 Tatsuya, Gastroenterology 122009
SVR rate (%) MEDIC CENTER HCV-1: Using response to determine duration of therapy 24 wk pegifn + RBV 48 wk pegifn + RBV 72 wk pegifn + RBV Patients with RVR at Wk 4 Slower responders 100 80 89 88 77 87 No RVR, pevr cevr 2 3-log 10 decline in HCV RNA at Week 12 60 40 38 38 64 47 20 18 25 0 110 170 123 62 49 52 PegIFN α-2b 1.5 μg PegIFN α-2b 1.5 μg/ PegIFN α-2b 1.5 μg + RBV 800 1,400 mg 1,2 PegIFN α-2a 180 μg/ + RBV 800 1,400 mg 4 + RBV 1,000 1,200 mg 3 21 52 PegIFN α-2b 1.5 μg/ PegIFN α-2a 180 μg/ + RBV 1,000 1,200 mg 3 16 15 PegIFN α-2b 1.5 μg/ + RBV 800 1,400 mg 5 1. Zeuzem S, et al. J Hepatol 2006;44:97-103; 2. Craxi A, et al. J Viral Hepat 2011:doi:10.1111/j.1365-2893.2011.01515.x; 3. Mangia A, et al. Hepatology, 2008; 47:43-50; 4. Pearlman BL, et al. Hepatology. 2007;46:1688-94; 5. Buti M, et al. Hepatology 2010;52:1201-1207.
Week 24: follow-up Fatigue HCV RNA: negative Weight: 68 kg AST: 98 IU/L; ALT: 76 IU/L; GGT: 195 IU/L WBC:3.86 x 10 9 /L; neutrophils: 40.3%, Eos: 3% Haematocrit: 39.5 %; haemoglobin: 11.5 g/dl Platelets: 98 x 10 9 /L AFP: 21 ng/ml Bilirubin-T: 1mg% Thyroid stimulating hormone: 0.9 miu/l US: Hepatitis, FibroScan: F4 (24 kpa)
ALT, AST, GGT increase, why? HBsAg: negative, AntiHBs: 120 IU/mL AntiHAV IgM: negative, AntiHAV total: positive ANA, AMA-M2, LKM1, ANCA: negative Alkaline phosphatase: normal MSCT: chronic hepatitis
What decision? 1. Continue treatment? 2. Stop treatment? 3. Hepatitis due to Interferon, Acetaminophen? Next step
Stop Acetaminophen-Continue treatment with Ursodeoxycholic acid +Vit C+Vit E Week 28 follow-up Feel better Weight: 68 kg AST: 120 IU/L; ALT: 66 IU/L; GGT: 175 IU/L WBC:3.12 x 10 9 /L; neutrophils: 39.3%, Eos: 1% Haematocrit: 38.5 %; haemoglobin: 11.2 g/dl Platelets: 92 x 10 9 /L AFP: 22 ng/ml Bilirubin-T: 0.8mg% Thyroid stimulating hormone: 0.7 miu/l
Week 36 follow-up HCV RNA: negative Weight: 66 kg AST: 70 IU/L; ALT: 54 IU/L; GGT: 95 IU/L WBC:3.53 x 10 9 /L; neutrophils: 38.1%, Eos: 1% Haematocrit: 39.1 %; haemoglobin: 11.2 g/dl Platelets: 90 x 10 9 /L AFP: 18 ng/ml Bilirubin-T: 1mg% Thyroid stimulating hormone: 0.5 miu/l US: Chronic hepatitis
Week 48 follow-up Fatigue HCV RNA: negative Weight: 65 kg AST: 68 IU/L; ALT: 42 IU/L; GGT: 90 IU/L WBC:3.34 x 10 9 /L; neutrophils: 37.1%, Eos: 1% Haematocrit: 38.2 %; haemoglobin: 10.9 g/dl Platelets: 70 x 10 9 /L AFP: 16 ng/ml Bilirubin-T: 1mg% Thyroid stimulating hormone: 0.4 miu/l US: Chronic hepatitis- FibroScan: 16 KPa
What would your management decision be now? 1. Stop treatment 2. Continue current treatment 3. Reduce Peginterferon and/or Ribavirin dose 4. Continue treatment with Erythropoietin
Week 60 follow-up Severe fatigue, tachycardiac HCV RNA: negative Weight: 62 kg AST: 69 IU/L; ALT: 58 IU/L; GGT: 92 IU/L WBC:3.20 x 10 9 /L; neutrophils: 37.2%, Eos: 1% Haematocrit: 38.6 %; haemoglobin: 10.8 g/dl Platelets: 69 x 10 9 /L AFP: 12 ng/ml Bilirubin-T: 0.8mg% Thyroid stimulating hormone: 0.005 miu/l
Week 60 follow-up Free T3: 12 pg/ml Free T4: 9.2 ng/dl Thydroid US: Hyperthydroidism Abdominal US: Chronic hepatitis
What would your management decision be now? 1. Stop treatment 2. Reduce Peginterferon and/or Ribavirin dose 3. Continue treatment with Erythropoietin 4. Work with an endocrinologist and continue treatment
Week 72 follow-up Feel better HCV RNA: negative Weight: 64 kg AST: 64 IU/L; ALT: 52 IU/L; GGT: 89 IU/L WBC:3.30 x 10 9 /L; neutrophils: 36.8%, Eos: 1% Haematocrit: 38.1 %; haemoglobin: 10.6 g/dl Platelets: 66 x 10 9 /L AFP: 8 ng/ml Bilirubin-T: 0.7mg% Ferritin: 1800 ng/ml
Week 72 follow-up Free T3: 4.4 pg/ml Free T4: 3.2 mui/l Thyroid stimulating hormone: 0.35 miu/l Abdominal US: Chronic hepatitis FibroScan: 14 KPa
24 weeks after stop treatment Feels weell Weight: 68 kg HCV RNA: Negative - AST: 28 IU/L ALT : 30 IU/L GGT:40 IU/mL - WBC: 4.25 10 9 /L N: 41 % - Hct: 39.2 % Hb:12.1 g/dl - Platelets: 125 10 9 /L - TSH: 1.22 miu/l FT3: 2.41pg/mL FT4: 1.55 ng/dl -Glycemia: 5.9 mmol/ml Creatinin: 0.9 mg/100 ml- Ferritin: 420 ng/ml US: hepatitis FibroScan: F3 (Fs= 8.8 KPa)
Clinical outcomes of HCV: Risk of mortality and HCC increase if HCV is not cured
Key learning points Chronic hepatitis C disease can be cured The important problems: *Consider the characters of patients carefully *What are the predictors for SVR? *How to choose a suitable regimen for treatment? *Consult with relative specialists It is not difficult to achieve a SVR when treating HCV genotype 1 with Peginterferon and Ribavirin if all of the above are applied.
Thank you!