MEDIC CENTER. Case 2

Transcription

1 Case 2

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)

3 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

4 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

5 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

6 Treatment regimen for this patient Peginterferon alfa-2a 180 mcg/week and ribavirin 1000 mg/day

7 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: /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

8 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: Katz et al, Cochrane Database Systematic Rev 2012;9:CD Liu CH et al, Antiviral Therapy 2012;17:477-84

9 SVR (%) MEDIC CENTER IL28B rs Polymorphisms and Response to PegIFN/RBV by HCV Genotype Genotype 1 Genotype 2/3 Genotype CC CT TT 20 0 Albert Friedrich Stättermayer et al., Clinical Gastroenterology and Hepatology Volume 9, Issue 4, Pages , April 2011

10 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: /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

11 What would your management decision be now? 1. Stop treatment 2. Continue treatment

12 % SVR MEDIC CENTER SVR of Patients with Late HCV RNA-Negativity 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

13 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 No RVR, pevr cevr 2 3-log 10 decline in HCV RNA at Week 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 PegIFN α-2b 1.5 μg/ PegIFN α-2a 180 μg/ + RBV 1,000 1,200 mg 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: /j x; 3. Mangia A, et al. Hepatology, 2008; 47:43-50; 4. Pearlman BL, et al. Hepatology. 2007;46: ; 5. Buti M, et al. Hepatology 2010;52:

14 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)

15 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

16 What decision? 1. Continue treatment? 2. Stop treatment? 3. Hepatitis due to Interferon, Acetaminophen? Next step

17 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

18 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

19 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

20 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

21 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: miu/l

22 Week 60 follow-up Free T3: 12 pg/ml Free T4: 9.2 ng/dl Thydroid US: Hyperthydroidism Abdominal US: Chronic hepatitis

23 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

24 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

25 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

26 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: /L N: 41 % - Hct: 39.2 % Hb:12.1 g/dl - Platelets: /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)

27 Clinical outcomes of HCV: Risk of mortality and HCC increase if HCV is not cured

28 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.

29 Thank you!