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Fatty Liver in HIV+ / HIV Research Politics, Aging - Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy
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Download the PDF here
from Jules: fatty liver & NASH in HIV has never received much attention despite from the early days, study below from 2002, there have been a series of indications & publications linking HIV, ARTs and fatty liver. WHY? Good question. It appears to me politics and vested interests is a factor that drives research in HIV. Why is cure getting more attention than aging/HIV? Perhaps part of the justification is the thinking that if we could eradicate HIV the aging phenomena, premature or accelerated aging, would disappear or be a great friend to older aging. This reflects not understanding the aging /HIV problem. After 20-30 years with HIV the damage on the body & organs has been done, the cumulative damage is not reversible. Eradication is not very likely certainly not soon. Functional cure would not eliminate HIV. So in this context it is clear to me at least that aging/HIV is big problem that needs and deserves much more attention, more funding, better research and services for older aging patients - than it gets. But for those who pay attention mostly to cure & PreP for that matter too, what drives them besides not understanding the dynamics of aging/HIV. Above I suggested politics & vested interests. A few years ago President Obama said we need to find a cure, he used his bully pulpit, immediately the NIH dedicated large sums of funding to cure. That's where the money funding is now & the attention at the NIH - on cure, and PrEP too. It certainly is "pop" ular now to talk about cure, it is the "hot" topic and very appealing, like "eye-candy", just like interruptions research 8-9 years ago was the "pop" eye candy, until it wasn't, after they found interruptions did damage & were not useful, which myself & others had said previously. Ending AIDS is now "pop eye-candy", very popular, very well funded, organizations & researchers go where the funding/money is. Aging/HIV is NOT "pop" eye-candy. In this society we don't value older people anyway but in HIV our aging/HIV+ are expendable. It's the step child of interests. End AIDS, not happening. Should we pursue End AIDS, cure & PrEP and support these issues, a resounding YES, but not at the expense of marginalizing the more important problem for HIV+ certainly in the USA, where 50% are over 50, 80% over 40-45; older aging HIV+ are often suffering disabilities and severe ravages of premature aging, with multi comorbidities & polypharmacy, cognitive impairment, worsened fractures & bone disease, worsening heart disease & diabetes - but I guess trying t address these problems with more focus, funding & services is beyond those in power. Remember 7-10 years ago researchers & the DAIDS could not find answers to lipodystrophy so they just abandoned their efforts, that is not much different than how older aging HIV+ are getting treated today. Why didn't we then expand the research effort - bring on NOH researchers, researchers from other fields, instead of like we do now confining the research effort to only the HIV research community. We need better, more focused research to better understand the science of aging in HIV and we need special support services for older aging patients & clinics, HRSA, RWCA where are you? We cant wait 5 years - OAR where are you? We need attention NOW.
Its estimated 30-40% of HIV+ have fatty liver (NAFLD) and studies suggest these rates may be higher than in HIV-negatives. BUT here is a study finding 67% fatty liver in HCV/HIV coinfected .....
67% Steatosis in HCV/HIV Coinfected: : Liver inflammation, HCV genotype 3, and BMI are associated with steatosis, a common finding in HCV-HIV-coinfected patients http://www.natap.org/2007/HIV/062007_02.htm
IWCADRH: Clinical Implications of Nonalcoholic Fatty Liver Disease in Patients with HIV Infection - (06/23/17)
CROI/2017:
Changes in Liver Fibrosis and Steatosis in HIV Mono-Infected patients over 24 months - 50% have fatty liver at average age of 46 - (03/28/17)
LIVER STEATOSIS AND FIBROSIS IN AT-RISK EUROPEAN HIV-MONOINFECTED PATIENTS - 64% with steatosis among those who had elevated LFTs and/or metabolic syndrome and/or lipodystrophy - (03/28/17)
The risk of cardiovascular disease and death over 10 years in HIV/HCV co-infected patients with and without steatosis ....mortality was high .....high rates of cardiovascular disease - (08/14/15)
Fatty Liver in HIV & HCV: Characterization of link between hepatic steatosis, insulin resistance, metabolic syndrome......http://www.natap.org/2009/EACS/EACS_21.htm
FATTY LIVER in HCV/HIV Coinfection-What is fatty liver?
plenary at CROI 2017 -FATTY LIVER DISEASE: A GROWING CONCERN
Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis - (05/22/17)
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Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy
Lipodystrophy & Fatty Liver from Early Study
http://www.natap.org/2002/Dec/120202_3.htm
(from Jules: The authors make the case that fat loss, not fat gain in viscera in belly, leads to fat in the liver and may be a causative factor in the development of insulin resistance in these patients)
Lipodystrophy was defined as self-reported symptoms of subcutaneous fat loss with/ without increased girth or buffalo hump. Patients were included in the lipodystrophy group (HAART+LD+, n = 25) after the investigators confirmed the self-reported findings.
"...Liver fat content has not been quantified previously in patients with HAART-associated lipodystrophy. We found liver fat content to be higher in the patients taking HAART and who had lipodystrophy than in patients taking HAART who did not have lipodystrophy or HIV-negative subjects. All patients were matched for age and weight..."
In conclusion, we have demonstrated increased hepaticfat content in HIV-positive men with HAART-associatedlipodystrophy when compared to healthy HIVnegativemen of similar age and BMI and to HIV-positivemen who had received HAART but notdeveloped lipodystrophy. Increased liver fat is closelycorrelated with features of insulin resistance and may
play a causative role in the development of insulinresistance in these patients.
The severity of the insulin resistance syndrome in patients with HAART-associated lipodystrophy is related to the extent of fat accumulation in the liver rather than in the intra-abdominal region. Fat accumulation in the liver may therefore play a causative role in the development of insulin resistance in these patients.
Liver fat content was significantly higher in the HAART+LD+ (8 ± 10%) than the HIV- (5 ± 7%; P < 0.05) or the HAART+LD- (3 ± 5%; P < 0.01) group. Liver fat content correlated with serum fasting insulin in the HAART+LD+ (r = 0.47; P < 0.05) and HIV- groups (r = 0.65; P < 0.001), but not with the amount of intra-abdominal fat. Within the HAART+LD+ group, serum insulin did not correlate with the amount of intra-abdominal fat. The HAART+LD+ group had a lower serum leptin concentration when compared to the two other groups. Features of insulin resistance, including hepatic fat accumulation, were not found in HAART+LD- group.
Serum insulin and C-peptide concentrations were significantly higher in the HAART+LD+ group than either in the HAART+LD- or the HIV- group. Serum insulin concentrations did not correlate with the amount of intra-abdominal fat within HAART+LD+ group (r = 0.26, not significant). The HAART+LD+ patients had significantly lower concentrations of serum HDL cholesterol and higher concentrations of serum triglycerides than the HAART+LD- patients or the HIV-negative subjects. Serum total cholesterol was significantly higher in the HAART+LD+ group (5.9 ± 1.1 mmol/l) than in the HAART+LD- group (4.8 ± 0.8 mmol/l; P < 0.01) or in the HIV- group (5.1 ± 1.0 mmol/l; P < 0.01). Serum ALT and AST concentrations were significantly higher in the HAART+LD+ group than in the HAART+LD- or the HIV- group, and serum GGT was significantly higher in the HAART+LD+ group than in the HIV-negative subjects. Blood lactate concentrations were similar in both HIV-positive groups and none of the patients had acidosis.
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