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HIV and The Liver: Forever Y oung?

HIV and The Liver: Forever Y oung?. Marina B. Klein, MD CM, MSc , FRCP(C) Infectious Diseases/Chronic Viral Illness Service McGill University Health Centre Montreal, Canada. Disclosures. Receipt of grants/research support: Merck, Schering-Plough , viiv

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HIV and The Liver: Forever Y oung?

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  1. 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

  2. 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

  3. 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

  4. 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)

  5. BRAIN HEART KIDNEYS LIVER PANCREAS(DM)

  6. Does Age Affect the Liver?

  7. Aging and the liver • Several age-related changes in liver have been documented in the elderly, including: • decline in liver volume and blood flow • moderate declines in the Phase I metabolism of drugs (but not CYP-450) • shifts in the expression of a variety of proteins • diminished hepatobiliaryfunctions • Functional consequences of these changes, if any, have not been clearly shown DL Schmucker. Exp Gerontology, 2005.

  8. 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.

  9. What’s wrong with this picture?

  10. Estimated numbers of Co-infected persons (worldwide)

  11. 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

  12. Fatty Liver Disease 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

  13. Cirrhosis HCV Hepatocellular carcinoma Alcohol

  14. 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

  15. Mitochondrial toxicity

  16. HIV ESLD Advancing Age

  17. 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

  18. 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

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