natural history of hepatitis c infectiondepts.washington.edu/hepstudy/presentations/... · natural...
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Kenneth E. Sherman, MD, PhD Gould Professor of Medicine
Director, Division of Digestive Diseases University of Cincinnati College of Medicine
Cincinnati, Ohio
Natural History of Hepatitis C Infection
Recorded on May 15, 2013
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Disclosure Information
� Research grants or contracts (awarded to his institution) from: Anadys, AbbVie, Bristol-Myers Squibb, Genentech, Gilead Sciences, Inc, Merck & Co, Inc, Vertex Pharmaceuticals, Inc
� Advisory board member or consultant to: Bioline, Kadmon, Merck & Co, Inc, MedPace, Janssen Therapeutics (formerly Tibotec), Roche Molecular
Disclosure Information (past 12 months)
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Outline
� Spontaneous clearance versus chronic infection � Variable outcomes of chronic infection � Predictors related to rate of progression of fibrosis
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Spontaneous Clearance Versus
Chronic Infection
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Spontaneous Clearance Versus Chronic Infection
� Outcome of acute infection ¡ Clearance of hepatitis C virus (HCV): 10%-35% ¡ Development of chronic HCV infection: 65%-90%
� Predictors affecting outcome of acute infection ¡ IL28B genotype ¡ Quasispecies diversification ¡ Size and source of inoculum ¡ Immune status ¡ Clinical features
÷ Development of jaundice
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IL28B
DL Ge et al. Nature. 2009;461(7262):399-401
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DL Thomas et al. Nature. 2009
OR 3.0 OR 3.1 OR 2.6
IL28B: Percentage of HCV Clearance by rs12979860 Genotype
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Genetic Variation in IL28B Explains Differences in HCV Recovery Rates in Diverse Ethnicities
Thomas DL et al. Nature. 2009.
Different frequencies in IL28B variants explain ethnic differences in HCV recovery rates
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Acute Hepatitis C
Chronic Hepatitis 75%-85 %
Cirrhosis 20 %
DiBisceglie. Hepatology. 2000.
20 y
ears
Decompensated 20% HCC 1%-4% per year
Natural History
HCC, hepatocellular carcinoma
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Variable Outcomes of Chronic Infection
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10 20 30 40 50 0
Mild
Moderate
Severe fibrosis
Cirrhosis: mild
Cirrhosis: severe
HCC 20%-33%
15%-33%
Years
Adapted from Afdhal. Sem Liver Disease. 2004.
Variable Outcomes of Chronic Infection
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Factors Impacting Rate of Progression of Fibrosis
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Predictors Related to Rate of Progression of Fibrosis
� Older age at infection � Male sex � Alcohol � HIV infection � Post-transplant � Quasispecies complexity � Presence of comorbid liver diseases
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Clinical Outcomes of Cirrhosis
� Portal hypertension ¡ Varices ¡ Ascites ¡ Hepatic encephalopathy ¡ Splenomegaly ¡ Thrombocytopenia
� HCC
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HCV in Patients With Cirrhosis, Risk of Decompensation and HCC
Fattovich et al. Gastroenterology. 1997.
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Summary
� Most people who are infected with HCV progress to a chronic disease state
� A variety of factors determines individual risk of clearance vs chronicity
� Chronicity leads to variable rates of fibrotic progression
� Cirrhosis leads to ¡ End-Stage Liver Disease ¡ HCC
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End
This presentation is brought to you by the International Antiviral Society-USA (IAS-USA) in collaboration with Hepatitis Web Study & the Hepatitis C Online Course
Funded by a grant from the Centers for Disease Control and Prevention