Incidence and Risk Factors for Steatosis Progression in Adults Coinfected With HIV and Hepatitis C Virus

The Johns Hopkins Hospital/University School of Medicine, Baltimore, Maryland 21287, USA.
Gastroenterology (Impact Factor: 16.72). 12/2010; 140(3):809-17. DOI: 10.1053/j.gastro.2010.11.052
Source: PubMed


Hepatic steatosis is a common histologic finding in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), although little is known about its natural history. We prospectively examined the natural history of steatosis in patients coinfected with HIV and HCV who attended an urban HIV clinic.
The study cohort consisted of 222 coinfected patients (87% black, 94% with HCV genotype 1 infection) who had at least 2 liver biopsies performed between 1993 and 2008. Biopsy specimens were scored by a single pathologist; samples were classified as having trivial (<5% of hepatocytes affected) or significant (>5%) levels of fat (steatosis). We characterized progression to significant levels of fat among patients whose first biopsy samples had no or trivial levels of fat, and regression among those with significant fat, using logistic regression.
Initial biopsy specimens from most patients (88%) had no or trivial amounts of fat. Among second biopsy samples, 74% had no or trivial fat and 13% had significant amounts of fat. The strongest risk factors for progression of steatosis were alcohol abuse and overweight/obesity; cumulative exposure to antiretroviral therapy between biopsies and high counts of CD4(+) T cells were associated with reduced progression of steatosis. Among the 28 patients whose initial biopsy specimen had significant fat levels, most (75%) regressed.
Antiretroviral therapy and high counts of CD4(+) T cells are associated with reduced progression of steatosis in patients coinfected with HIV and HCV. Efforts to diagnose and prevent steatosis should focus on persons with a high body mass index and excessive alcohol intake.

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Available from: Tinsay Woreta, Jan 19, 2015
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    • "Liver steatosis constitutes one of the outstanding manifestations of insulin resistance in hepatitis C virus (HCV) infection. HCV by itself -especially genotype 3- may lead to liver steatosis, but obesity and concomitant alcohol abuse are the main factors involved.[18] The "two hit theory" sustains that cytokine activation and increased lipid peroxidation contribute to the progression of simple steatosis to steatohepatitis.[19] "
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    ABSTRACT: Sclerostin inhibits osteoblast functions, differentiations, and survival rates. As an endogenous inhibitor of the Wnt/β-catenin pathway, the sclerostin should be related to decreased bone masses, although several studies indicate opposite results. In addition, it may be related to insulin resistances and carbohydrate metabolisms, a relation shared with other markers of bone metabolisms, such as osteocalcin. Hepatitis C virus (HCV) infected patients may present osteoporosis, and frequently show liver steatosis, which is a consequence of insulin resistance. The behaviour of sclerostin in these patients is yet unknown. The aim of this work is to analyse the relationships between serum sclerostin and osteocalcin levels and bone mineral density (BMD), liver functions, the intensity of liver steatosis and biochemical markers of bone homeostasis and insulin resistance in HCV-infected patients. Forty HCV patients with 20 years of age and gender-matching controls were included in this study and underwent bone densitometry. Serum sclerostin, osteocalcin, collagen telopeptide, adiponectin, leptin, insulin, resistin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined. Liver fat was histomorphometrically assessed. Sclerostin levels were slightly higher in patients than in controls, and were directly related to BMD at different parts of the skeleton, also to the serum telopeptide, and to the liver steatosis and TNF-α. On the contrary, osteocalcin showed a significant direct relationship with serum adiponectin, and an inverse one with IL-6. Serum sclerostin levels were within the normal range in HCV patients, and correlated directly with BMD and serum telopeptide. In addition, the relationships of sclerostin and osteocalcin with variables associated with insulin resistance suggested the role of bones for intermediary metabolisms.
    02/2014; 21(1):69-75. DOI:10.11005/jbm.2014.21.1.69
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    • "Whereas most of our patients, and those included in the study of Bauerle et al. [37], were Caucasian and carrying HCV genotype 3, other studies have included a high proportion of Africo-American patients (47-94%) and patients infected with HCV genotype 1 [38-45]. It is well-known that HCV-infected Black people have a lower prevalence of HS than Caucasian [41,45-47], probably related to lower visceral adipose tissue [16,22]. "
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    ABSTRACT: In HIV and hepatitis C virus (HCV) coinfected patients, the role of antiretroviral therapy (ART) on hepatic steatosis (HS) remains controversial. HIV/HCV coinfected patients receiving ART and previously untreated for HCV who underwent a liver biopsy were included. Cumulative duration of exposure to each antiretroviral was recorded up to liver biopsy date. Logistic regression analyses evaluated factors associated with steatosis and its severity. 184 patients were included: median age 41 years, 84% male, 89% Caucasian, 61% with a past history of intravenous drug use. HCV genotypes were 1 (55%), 2 (6%), 3 (26%), and 4 (13%). Median HCV-RNA was 6.18 log10 IU/ml. HIV-RNA was undetectable (<400 copies/ml) in 67% of patients. Median CD4 count was 321/mm3. All patients had been exposed to nucleoside reverse transcriptase inhibitors (median cumulative exposure 56 months); 126 received protease inhibitors (23 months), and 79 non-nucleoside reverse transcriptase inhibitors (16 months). HS was observed in 102 patients (55%): 41% grade 1; 5% grade 2, and 9% grade 3. In multivariate analysis, HCV genotype 3 and HCV viral load were moderately associated with mild steatosis but strongly with grade 2-3 steatosis. After adjustment for the period of biopsy, no association was detected between HS and exposure to any antiretroviral class or drug, or duration of ART globally or comparing genotype 3 to others. Among our ART-treated HIV-HCV cohort predominantly infected with genotype 1, 55% of patients had HS which was associated with HCV-related factors, but not ART class or duration of exposure.
    BMC Research Notes 04/2012; 5(3):180. DOI:10.1186/1756-0500-5-180
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