Different rates of underlying steatohepatitis in previous studies may account for the contradictory results on the relationship between HS and fibrosis in coinfected patients. This study has a few limitations. First, HS may change signaling pathway fast in response to the modification of some factors, such as alcohol intake, overweight, or drugs. These changes could be missed by a paired biopsy study, particularly if the time between biopsies is very long. Importantly, under- or overdiagnosing the incidence of HS in liver biopsies resulting from changes in such modifiable factors may be a relevant reason for discrepant results among studies or for lack of detection of some associations. This limitation is inherent in every liver

biopsy-based study. Additionally, the use of scores to classify HS precludes the detection of smaller changes in HS, within each HS category. The only theoretical solution to these drawbacks would RG7422 manufacturer be a prospective study with a frequent schedule of noninvasive assessments of HS using a reliable procedure. Second, alcohol intake was self-referred by patients. Probably because of this, we did not find any association between alcohol and HS. In this regard, previous cross-sectional studies also failed to find this relationship.1,

4-6, 9 In fact, history of alcohol abuse was associated with HS progression in a study on sequential liver biopsies, but present reporting was not.15 Third, some antiretroviral drugs used during the period of study have become obsolete, particularly dideoxynucleoside analogs and unboosted protease inhibitors. A number of newer antiretroviral drugs are available to combine that may have no mitochondrial toxicity and 上海皓元 a better metabolic profile and thus potentially lead to lesser HS. Thus, data on the HS associated with those newer drugs are needed. Fourth, patients who accept to undergo repeated liver biopsies are highly selected. Usually, these patients are those more compliant with follow-up. Clinicians may indicate a follow-up biopsy if liver disease progression is suspected. Thus, rates of HS and steatohepatitis might be overestimated by paired liver biopsy studies as the

study herein reported on. However, the frequency of HS in the present study is in agreement with previous cross-sectional studies.1-11 Moreover, rates of steatohepatitis were similar to those from a previous cross-sectional report.5 Finally, this study’s results may not be applicable to other groups of patients, because very few overweight or obese individuals were included and the racial background of the study subjects was only Caucasian. In summary, HS is frequently detected in HIV/HCV-coinfected patients with and without ART and high rates of progression to severe HS are observed in them. This is a major concern, given that among individuals with HS, those with features of steatohepatitis are at increased risk of fibrosis progression.