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Longer D-Drug Exposure and Higher Glucose Boost Risk of Steatosis Progression
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
Longer exposure to antiretrovirals inflated the risk of hepatic steatosis progression in a study of 146 people in Spain coinfected with HIV and hepatitis C virus (HCV) [1]. The now little-used dideoxynucleosides were the only antiretrovirals that independently raised progression risk, as did rising glucose levels. But these investigators found little evidence of steatosis regression in their study group.
A cross-sectional 222-person US study documented steatosis in 23% of HIV/HCV-coinfected people and steatohepatitis in 30%, both of which raised the risk of advanced fibrosis [2]. A separate longitudinal US study of 222 HIV/HCV-coinfected patients found lower hepatic steatosis prevalence at baseline than in previous studies, lack of progression in most patients, and a lower progression risk in people taking antiretrovirals [3]. To add to the understanding of steatosis progression and predictors in coinfected people, researchers across Spain planned this study.
This retrospective analysis involved all HIV-positive people in participating hospitals who had active HCV infection, two liver biopsies separated by at least 1 year, and no autoimmune, malignant, biliary, or vascular liver disease. The primary outcome was progression of 1 or more grades in the Brunt score of hepatic steatosis.
The 146 study participants had a median age of 38 years (interquartile range 33 to 41), 107 (73%) were men, and 125 (86%) were injection drug users. Thirty-one people drank more than 50 g of alcohol daily, and median body mass index stood at 22.5 kg/m(2) (IQR 21.9 to 23.4). Most people (80%) were on antiretroviral therapy, and 60% overall had an undetectable HIV load. Median CD4 count measured 495 (IQR 338 to 660). Most people (58%) had HCV genotype 1, followed by genotype 3 in 20% and genotype 4 in 13%.
Baseline fibrosis stage was 0 in 20%, 1 in 34%, 2 in 18%, 3 in 20.5%, and 4 in 7.5%. From baseline to follow-up, hepatic steatosis grade rose significantly (P < 0.001):
Change in steatosis grade from first to follow-up biopsy with HIV/HCV:
-- Grade 0 (no steatosis): 40% at baseline, 23% at follow-up
-- Grade 1: 39% at baseline, 44% at follow-up
-- Grade 2: 15% at baseline, 21% at follow-up
-- Grade 3: 5.5% at baseline, 13% at follow-up
Only 8% of study participants experienced steatosis regression during follow-up, 51% had no change, 36% had progression of 1 grade, and 5% had progression of 2 or more grades. Proportions of patients with steatosis progression rose with longer use of dideoxynucleosides (didanosine stavudine), lamivudine, and efavirenz:
Hepatic steatosis progression rates with HIV/HCV:
Dideoxynucleosides (didanosine or stavudine):
-- 2 to 4 years: 36%
-- Over 4 years: 88%
Lamivudine:
-- Under 2 years: 38%
-- 2 to 4 years: 42%
-- Over 4 years: 53%
Efavirenz:
-- Under 2 years: 22%
-- 2 to 4 years: 38%
-- Over 4 years: 88%
In multivariate analysis, however, only longer dideoxynucleoside use raised the risk of steatosis progression of 1 or more grade. For each additional year of dideoxynucleoside therapy, steatosis progression risk jumped 50% (adjusted odds ratio [AOR] 1.5, 95% confidence interval [CI] 1.2 to 1.8, P < 0.001). The only other variable that independently affected progression risk was every 10 mg/mL increase in fasting plasma glucose, which upped the risk 40% (AOR 1.4, 95% CI 1.04 to 1.9, P = 0.024).
Median nonalcoholic fatty liver disease activity score (NAS) was 3 (IQR 3 to 4) at the first biopsy and 4 (IQR 3 to 4) at the follow-up biopsy. Twenty-four people (16%) had steatohepatitis at the first biopsy, as did 27 (18%) at follow-up, a nonsignificant change (P = 0.6). Steatohepatitis persisted in 9 of 24 people (38%) with baseline steatohepatitis. Among the 122 people without steatohepatitis at their first biopsy, 18 (15%) had steatohepatitis at follow-up.
Fibrosis progression of 1 or more stages was the only variable independently associated with persistence or progression of steatohepatitis, more than doubling the risk (AOR 2.4, 95% CI 1.01 to 5.7, P = 0.047). Eleven people (14%) taking antiretrovirals for fewer than 4 years and 10 (25%) taking antiretrovirals for 4 or more head had persistence or progression of steatohepatitis, but this difference fell short of statistical significance (P = 0.119).
The researchers concluded that hepatic steatosis progression occurs often in HIV/HCV-coinfected people and that regression is rare. They stressed that steatohepatitis bolsters the risk of fibrosis progression in people coinfected with HIV and HCV.
References
1. Macias J, Berenguer J, Japon M, et al. Cumulative exposure to ARV drugs leads to progressive hepatic steatosis among HIV/HCV-co-infected patients. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 781. http://www.retroconference.org/2012b/PDFs/781.pdf.
2. Sterling RK, Contos MJ, Smith PG, et al. Steatohepatitis: risk factors and impact on disease severity in human immunodeficiency virus/hepatitis C virus coinfection. Hepatology. 2008;47:1118-1127. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394857/?tool=pubmed.
3. Woreta TA, Sutcliffe CG, Mehta SH, et al. Incidence and risk factors for steatosis progression in adults coinfected with HIV and hepatitis C virus. Gastroenterology. 2011;140:809-817. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073565/?tool=pubmed.
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