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Hepatitis C Genotype 4 Real life Clinical Challenges Sanaa Kamal Nabil Antaki

During his annual physical in Dec 2007, Mr. A, a 42 y old pilot, presented with elevated liver enzymes and positive antibodies to HCV.He had no symptoms. BMI 27His physical examination revealed no abnormalities and his liver was not enlarged. His blood picture, renal profile, thyroid profile w

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Hepatitis C Genotype 4 Real life Clinical Challenges Sanaa Kamal Nabil Antaki

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    1. Hepatitis C Genotype 4 Real life Clinical Challenges Sanaa Kamal Nabil Antaki

    2. During his annual physical in Dec 2007, Mr. A, a 42 y old pilot, presented with elevated liver enzymes and positive antibodies to HCV. He had no symptoms. BMI 27 His physical examination revealed no abnormalities and his liver was not enlarged. His blood picture, renal profile, thyroid profile were within normal His physical performed December 2006 was normal

    3. He was recently married. He is frustrated He will be subjected to another medical examination after 3 months. He could not recall how, when or where he got the infection

    6. What to do at this time? Request a liver biopsy Do an ultrasound only Request more investigations Wait and see

    14. Terminology RVR :Rapid virological response (4 weeks) EVR :Early virological response (12 weeks) -Complete EVR : HCV RNA positive at Wk 4 but negative at Wk 12 - Partial EVR: HCV RNA positive at WK 4 and 12 but ? 2 log10 IU/mL drop from baseline at Wk 12 SVR:Sustained virological response NR :Non response; Transient virological response; relapse (20%) or breakthrough (10%)

    15. Rapid Virological Response Genotype 1 216 patients 51 (24%) had RVR SVR associated with RVR and lower HCV viral load (< 600,000 IU/ml) RVR portends an 89% probability of SVR after 24 weeks of treatment

    16. Rapid Virological Response Genotype 2 – 3 283 patients: RVR as a guide for 12w or 24w Shorter course as effective as 24w if patients are negative by week 4 Higher relapse rate (8.9 Vs. 3.6%) PEG-IFN alpha 2b (1.0 microg/Kg/week) Results consistent with a Norwegian trial

    17. Rapid Virological Response Genotype 4 318 patients: RVR, EVR as a guide for 24 w, 36 w or 48w

    18. Kamal et al, Hepatology. 2007 Dec;46(6):1732-40

    19. RVR HCV Genotype 4 66 patients with G4, Peg IFN a 2a and RBV RVR: 45% 26 (86.7%) of those achieved a SVR No relation: with degree of Fibrosis with baseline viral load with dose of RBV

    20. Main Findings In per-protocol analysis, 80.4% SVR rate in patients with RVR (115/143)

    21. Distribution of Virologic Response Rates Retrospective analysis from 3 large trials (N = 1383) PegIFN alfa-2 + RBV RBV 800 mg/day for 24 wks in GT 2/3 RBV 1000-1200 mg/day for 48 wks in GT 1/4

    22. SVR in Patients Who Achieved an RVR

    23. Kamal et al, Hepatology. 2007 Dec;46(6):1732-40 Rapid virologic response is a clinically useful tool for determining the duration of treatment in chronic hepatitis C genotype 4. 24 weeks therapy with peginterferon-alpha-2a and ribavirin seems sufficient for patients with chronic hepatitis C genotype 4 who have a rapid virologic response.

    24. RVR: Conclusions Chronic Disease: Genotype 1, 4: useful for 24 week strategies Genotype 2 – 3: unclear the utility HIV - HCV: Encouraging marker

    25. Predictive factors of Low SVR

    26. Case Presentation 2 Mr. N, an 49-year-old Egyptian American engineer living and working in the US since 12 years. HCV (G4) accidentally detected since 8 years He had received repeated blood transfusion 15 years before following a traffic accident. He is diabetic on oral medications for diabetes mellitus. He is obese. His BMI: 30

    27. Previous therapy He has been previously treated in 2004 with 48 weeks of PEG-IFN a-2b and ribavirin but relapsed. He achieved an early virologic response (EVR). At one point, his lab results showed anemia. He had his ribavirin dosage repeatedly reduced until his anemia improved. He was able to complete 48 weeks of treatment and achieved an ETR and SVR. In 2007, HCV-RNA was detectable

    28. Second presentation Dec. 2007 ALT: 70 U/L, AST: 60 U/L Albumin: 3.9 g/dL Blood picture: Hb: 13 gm%, Platelet count: 130,000, WBCs: 8,400. Serum HCV RNA: 800 000 IU/mL Genotype 4

    32. What to Do? Treat for 24 weeks Treat for 36 weeks Treat for 48 weeks Stop the treatment Other choices or suggestions

    33. What about extending treatment?

    34. Extending treatment: Ferenci et al, 2008 Patients with no RVR but EVR: Group A : 48 W Group B : 72 W Patients with no EVR: Group C: 72 W

    35. Extending treatment Group A and B had similar SVR: 52% and 51% Relapse rate lower in group B (19%) vs. 33% in group A Complete EVR: SVR group A (71%) group B (78%) Partial EVR: SVR group A (31%) group B (35%)

    36. Case Presentation 3

    37. Mr. H, a 21 y old man accidentally discovered elevated liver enzymes and positive antibodies to HCV during check-up. His physical examination revealed no abnormalities and his liver was not enlarged. His blood picture, renal profile, thyroid profile were within normal He had no symptoms

    42. Case Study #4 38-year-old Greek man Diagnosed with HIV since 2005 Doing well on HAART He stopped using drugs (heroin). He has recently separated from a partner of 3 years.

    43. Case Study # 4 July 2007 ALT: 217 U/L HCV-AB positive HCV RNA: 1.2 M U/ml Genotype 4 Liver biopsy: Grade 8, stage 2 CD4+: 520

    44. What do you want to know? Transmission Alcohol use Depression/Antidepressants Treatment Choices

    45. HCV/HIV Coinfection HIV accelerates Hep C liver disease (may cut time to cirrhosis in half!) Hep C may impair immune reconstitution after HAART HCC may occur at an earlier age with coinfection

    46. HCV-G4/HIV Coinfection Treatment of Chronic HCV-4 in HIV patients is less successful than treatment of chronic hepatitis C in HCV monoinfected individuals. SVR rates: IFN- monotherapy: 11.1% IFN- plus ribavirin: 9.1% PEG-IFN plus RBV: 22.7% Legrand-Abravane et al, J Med Virol 2005;77:66-69. SVR 15% Soriano et al, Antiviral Ther 2005;10:167-170. .

    47. HIV/HCV Treatment Predictors of success in achieving a sustained viral response: CD4 count greater than 500 HIV RNA levels below 10,000 copies No alcohol consumption

    48. Treatment Decisions Treat Hep. C first ? (if HIV stable, if CD4 count good) Treat HIV first? (if immune compromised)

    49. HIV/HCV Co-infection Study

    50. Sustained Virologic Response*

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