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HIV and The Liver: Forever Young?
Marina B. Klein, MD CM, MSc, FRCP(C)Infectious Diseases/Chronic Viral Illness Service
McGill University Health CentreMontreal, Canada
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Disclosures
• Receipt of grants/research support:– Merck, Schering-Plough, viiv– Canadian Institutes of Health Research, National
Institute of Health Research, Fonds de recherches en santé du Québec, CIHR Canadian HIV Trials Network
• Receipt of honoraria or consultation fees: – viiv, Gilead, Merck
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Case
• 56 y/o male• HIV+ since 1989• Previous therapy: AZT, DDI, d4T, NVP, SAQ,
lopinavir/rtonavir, T-20….• Currently darunavir/ritonavir/etravirine,
raltegravir• VL 210, CD4 690.• Severe lipodystrophy, cirrhosis, recent CABG X5
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THE LIVER• The liver is a resilient,
maintenance-free organ• It's easy to ignore - until
something goes wrong• Often, people with liver
disease will be completely unaware because they may have few, if any, symptoms
• The liver continues to function even when two thirds of it has been damaged by scarring (cirrhosis)
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LIVERBR
AIN
KIDNEYS
PANCREAS (DM)
HEART
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Does Age Affect the Liver?
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Aging and the liver
• Several age-related changes in liver have been documented in the elderly, including:a. decline in liver volume and blood flowb. moderate declines in the Phase I metabolism of drugs (but
not CYP-450)c. shifts in the expression of a variety of proteinsd. diminished hepatobiliary functions
• Functional consequences of these changes, if any, have not been clearly shown
DL Schmucker. Exp Gerontology, 2005.
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Aging and the liver• Other more subtle changes may contribute to
reduced hepatic regenerative capacity, shorter post-liver transplant survival and increased susceptibility to liver diseases– muted responses to oxidative stress– reduced expression of growth regulatory genes– diminished rates of DNA repair— particularly in
the mitochondrial genome– telomere shortening
DL Schmucker. Exp Gerontology, 2005.
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What’s wrong with this picture?
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Estimated numbers of Co-infected persons (worldwide)
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• Place map
• Alcohol use extremely common in HIV+ – 50% moderate drinkers and >10% classifiable as hazardous drinkers in a
variety of cohorts• Heavy alcohol linked to a number of adverse outcomes
– non-adherence, disease progression, cirrhosis, mortality
Alcohol
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• Non-alcoholic fatty liver disease (NAFLD), can evolve into non-alcoholic steato-hepatitis (NASH), cirrhosis and ultimately hepatic failure
• Increases risk for diabetes and coronary artery disease
Fatty Liver Disease
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Cirrhosis
HCV Alcohol Hepatocellular carcinoma
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A hidden epidemic?
• 1417 active HIV+ patients without viral hepatitis 2011-2012 at the McGill University Health Centre.
• The majority of individuals identified as having fibrosis were >45 years
•
Sebastiani , CAHR 2013
Heaptic steatosis Index NAFLD FIB-4>3.50
5
10
15
20
25
30
35
40
45
% PATIENTS WITH POSSIBLE LIVER DISEASE
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Mitochondrial toxicity
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Drug Toxicity
AlcoholSteatosisHIV
Advancing Age ESLD
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Conclusions: Research Needs• Define contribution of various non-hepatitis related
factors to liver disease in HIV and role of aging in this process
• To accomplish this:– Focus on non-hepatitis related liver disease– Better monitoring and diagnostic tools– Methods for dealing with complex interactions of various
factors and co-morbidities– Understand underlying mechanisms– Evaluation of interventions to alter liver disease
progression
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In the meantime…Keep your liver healthy (and young)
• Get tested (and treated) for HCV/HBV• Get vaccinated (HAV)• Moderate alcohol consumption• Avoid hepatotoxic drugs • Exercise and have a healthy diet• No evidence that antioxidant supplements
have significant impact on liver-related mortality (RR 0.89, 95% CI 0.39 to 2.05)*
*Cochrane Database Syst Rev. 2011