Transcript HIV and The Liver

HIV and The Liver:
Forever Young?
Marina B. Klein, MD CM, MSc, FRCP(C)
Infectious Diseases/Chronic Viral Illness Service
McGill University Health Centre
Montreal, Canada
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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
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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Kuala Lumpur, Malaysia , 30 June - 3 July 2013
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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HEART
LIVER
PANCREAS
(DM)
KIDNEYS
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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 flow
b. moderate declines in the Phase I metabolism of drugs (but
not CYP-450)
c. shifts in the expression of a variety of proteins
d. 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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Alcohol
• 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
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Fatty Liver Disease
• Non-alcoholic fatty
liver disease (NAFLD),
can evolve into nonalcoholic steatohepatitis (NASH),
cirrhosis and ultimately
hepatic failure
• Increases risk for
diabetes and coronary
artery disease
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Cirrhosis
HCV
Alcohol
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Hepatocellula
r 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
•
% PATIENTS WITH POSSIBLE LIVER
DISEASE
45
40
35
30
25
20
15
10
5
0
Heaptic steatosis Index
NAFLD
FIB-4>3.5
Sebastiani , CAHR 2013
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Mitochondrial toxicity
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Drug
Toxicity
HIV
Steatosis
Alcohol
ESLD
Advancing Age
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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)
•
•
•
•
•
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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
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