HIV and The Liver: Forever Y oung?

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

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


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


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


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)


LIVERBR

AIN

KIDNEYS

PANCREAS (DM)

HEART


Does Age Affect the Liver?


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.


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.


What’s wrong with this picture?


Estimated numbers of Co-infected persons (worldwide)


• 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


• 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


Cirrhosis

HCV Alcohol Hepatocellular carcinoma


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


Mitochondrial toxicity


Drug Toxicity

AlcoholSteatosisHIV

Advancing Age ESLD


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


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

HIV and The Liver: Forever Y oung?

Documents

Transcript of HIV and The Liver: Forever Y oung?