Hepatic steatosis has emerged as a major comorbidity in HIV-HCV coinfected patients [13
]. In this retrospective observational study of 184 HIV-HCV coinfected patients ART-treated but untreated for HCV at the time of liver biopsy, HS was present in about half patients (55%), which is similar to rates of 24-75% found in other studies of HIV-HCV coinfected and HCV monoinfected patients [12
]. In multivariate analysis, HS and its severity were only significantly associated with HCV genotype 3 and HCV viral load. Neither the type of ART, nor their prolonged duration of exposure with a median of near five years were related to steatosis. Moreover, ART have no differential effect on occurrence of HS according to the genotype 3 compared to others.
We confirmed previously data of higher HS associated with genotype 3 [23
]. Here, the rate of severe HS (14%) was higher in our study compared with 2-9% found in US studies in HIV-HCV coinfected individuals [12
], but was similar with rates found in other studies [37
], in particular with those conducted in France [39
]. Several reasons may explain these discrepancies. Whereas most of our patients, and those included in the study of Bauerle et al
], 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
]. It is well-known that HCV-infected Black people have a lower prevalence of HS than Caucasian [41
], probably related to lower visceral adipose tissue [16
HS is a frequent histological finding in patients with chronic hepatitis C virus infection, particularly among those infected with genotype 3 strain [24
]. The prevalence of 26% of genotype 3 in our study was similar to the prevalence of 18% reported in the French HepaVIH cohort [50
]. It has been postulated that genotype 1 is associated with metabolic steatosis rather than viral steatosis developed through a direct cytopathologic effect observed especially in genotype 3 infected patients [51
]. When we examined the factors impacting the level of steatosis on ART patients, genotype 3, and high HCV viral load were two independent factors associated with HS in accordance with previous studies [15
]. Both factors moderately increased the risk of mild steatosis, but were strongly associated with severe steatosis (grade 2 or 3).
Other factors such as greater age [18
], higher body mass index (BMI) [12
], hyperglycemia [12
], lower cholesterolemia [17
], and presence of lipodystrophy [17
] have also been found to be independently associated with steatosis in coinfected patients. In our study, patients with metabolic syndrome were not more likely to present HS. However, only seven patients had diabetes, and this limited sample size could have prevent to study this risk factor. Moreover, as expected, exposure to PIs and stavudine, were associated with elevated triglycerides (p
=0.08 and p
<0.0001, respectively), but this metabolic abnormality was not a risk factors of HS in our ART-experienced population. According to the lack of data about HOMA scoring, weight and BMI, we probably missed the impact of metabolic steatosis in genotype other than 3 [23
]. Other limitation of our retrospective study is lack of information about alcohol consumption. Nevertheless, as described by Machado et al.
, metabolic syndrome and alcohol were not associated to HS. BMI was considered an increasing risk factor but with small magnitude and diabetes as a possible risk factor with no data for HOMA scoring [16
]. Moreover, the higher percentage of genotype 3 reflect the association between HS and HCV viral parameters.
Many antiretroviral drugs have been associated with hepatic damage [57
]. It has been suggested that steatosis due to an accumulation of fatty acids in the hepatocytes could be a consequence of mitochondrial dysfunction, secondary to drugs or viruses inducing oxidative stress [60
]. The effect of the drug class and drugs within classes on HS in HIV-HCV coinfected patients remain unclear. Previously, some studies reported no significant association between HS and ART as in our study [12
]. When focusing on the use of stavudine, a medication closely linked with HS and lipodystrophy syndrome resulting from mitochondrial damage, Sulkowski et al.
] found that stavudine exposure was a risk factor for steatosis like in the study of Borghi et al., whereas no such association was found for this drug as well as the D-drug group of antiretrovirals (didanosine, zalcitabine) in other studies [23
]. Recently, in a meta-analysis of the risk factors associated with HS in HIV-HCV patients, Machado et al.
failed to find any association with antiretrovirals of any class and HS as well as in our study [16
]. Moreover, Woreta et al., showed in a study including a majority of Black patients (87%) with 94% genotype 1, the lack of association with antiretroviral drugs with a median cumulative drug exposure similar to ours [41
]. Despite its relatively small sample size, our study had a statistical power of 80% to detect an increased risk of steatosis of 3 for the antiretroviral drugs used less frequently such as abacavir, tenofovir and lopinavir. We could hypothesize that discrepancies with other studies were linked to the differential prevalence of Caucasion subjects, of metabolic characteristics and frequency of genotype 1 and 3. Borghi et al
. evocated a putative role of ART in the occurrence of HS in patients infected with genotypes other than 3 [23
] but in our study, the impact of ART on HS was not different between genotype 3 and the others.
In conclusion, for our Caucasian cohort predominantly infected with genotype-HCV 1, hepatic steatosis in HIV-HCV coinfected patients receiving antiretroviral therapy is associated with HCV-related factors particularly in genotype 3 patients but not antiretrovirals. Nevertheless, as showed in our study, ART seems play a minor role in HS since the choose and use of more "metabolically friendly" antiretroviral drugs. Overall, we found only viral parameters, HCV genotype 3, and HCV RNA value, which were strongly associated with HS, particularly a severe steatosis. Among HIV-HCV co-infected patients receiving ART and who had never been treated for HCV, neither the type of drugs nor the duration of exposure was related to HS whatever the genotype.