Treatment of Patients with Decompensated Cirrhosis due to Chronic Hepatitis C: Results with a Low Ac

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Treatment of Patients with Decompensated
Cirrhosisdue to Chronic Hepatitis CResults
with a Low AcceleratingDose Regimen (LADR)of
Antiviral Therapy
Gregory T. Everson, M.D. Professor of
Medicine Director of Hepatology University of
Colorado Health Sciences Center Denver, CO USA
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LADR RationaleImprove Tolerance to IFN
RBVTachyphylaxis to Side EffectsReduce Severity
of Cytopenias
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In Advanced HCV 1. Clear HCV RNA 2. Prevent
Post-transplant Recurrence 3. Stabilize, or
improve, liver disease and clinical course
Specific Aims
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Subjects (N 124)
67 of patients with EGD (49/73) had varices.
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LADR Protocol

• LADR
• Initial IFN alfa-2b, 1.5 MIU TIW, (n119) or
  PegIFN alfa-2b, 0.5 µg/kg/wk, (n5) RBV 600
  mg/d
• 2 weeks Increase IFN or PegIFN to full dose
• 4 weeks Increase RBV by 200 mg/d weekly
• CBC and biochemistry Q 2 weeks
• HCV RNA Q 3 months
• Goal
• Full doses of IFN, PegIFN, and RBV

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Genotype is a Major Determinant of Virologic
Response
of Patients
Virologic Response
Geno 1 vs Non-1 Plt.0001 for both EOTR and SVR
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SVR Interaction of Genotype and Treatment
of Patients with SVR
Treatment Course
Effect of Treatment Course Plt.0001 for geno 1,
PNS for non-1
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Complications (22 in 15 Pts)
Diabetes mellitus, pulmonary embolus, severe
thrombocytopenia --- one each.
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Cytopenia Prior to and On Therapy
of Patients
Cell Counts
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Results With Liver Transplantation (Out of 47
Transplanted Patients)
HCV RNA
Of the three who relapsed -- one was genotype 4,
completed a full course, and was transplanted 6
weeks later. Analysis of blood at day of
transplant revealed RNA. Another completed
only 6 weeks of Rx prior to urgent LTx for
hepatoma. The third patients treatment course
was interrupted by TACE Rx.
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Effect of SVR on Outcome
SVR N 30
No SVR N 94
LTx 12
No LTx 59
LTx 35
No LTx 18
(4 Lost to f/u)
Dead 2
Dead 13
Dead 7
Dead 4
ReRx 0 Prog HCV 0 Stable 10
ReRx 19 Prog HCV 32 Stable 10
(SVR 1)
ReRx 11 Prog HCV 21 Stable 7
(SVR 3)
ReRx 0 Prog HCV 0 Stable 14
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LADR 1. Clears HCV RNA 2. Prevents
Post-transplant Recurrence 3. Stabilizes, or
improves, liver disease and clinical course
Conclusions