Publications

Non-alcoholic steatohepatitis (NASH) is a disorder marked by alterations in hepatic lipid homeostasis as well as liver injury in the form of cell death, inflammation and fibrosis. Research into the pathophysiology of NASH is dynamic. New concepts from the fields of cell biology, microbiology, immunology and genetics are being tested for their applicability to NASH; discoveries in each of these areas are enriching our understanding of this complex disease. This review summarizes how recent developments from the bench and bedside are merging with more traditional concepts to reshape our view of NASH pathogenesis. Highlights include human studies that emphasize the role of lipogenesis in NASH and experimental work uncovering a role for the inflammasome in NASH. Genetic predispositions to NASH are being clarified, and intestinal microbiome is emerging as a determinant of fatty liver. These unique ideas are now taking their place within an integrated picture of NASH pathogenesis.

Episodic (less than weekly) drug use and binge drinking increase HIV-related sexual risk behaviors among men who have sex with men (MSM), yet no evidence-based interventions exist for these men. We describe an adaptation process of the Personalized Cognitive Counseling (PCC) intervention for utilization with high-risk, HIV-negative episodic, substance-using MSM. Participants (N = 59) were racially diverse, and reported unprotected anal intercourse and concurrent binge drinking (85%), use of poppers (36%), methamphetamine (20%) and cocaine (12%). Semi-structured interviews with 20 episodic, substance-using MSM elicited sexual narratives for engaging in unprotected anal intercourse while using alcohol or drugs. Emergent qualitative themes were translated into self-justifications and included in a revised PCC self-justification elicitation instrument (SJEI). The adapted SJEI was pretested with 19 episodic, substance-using MSM, and the final adapted PCC was pilot-tested for acceptability and feasibility with 20 episodic, substance-using MSM. This process can be used as a roadmap for adapting PCC for other high-risk populations of MSM.

OBJECTIVE

Tenofovir disoproxil fumarate is a widely used antiretroviral for HIV infection that has been associated with an increased risk of chronic kidney disease (CKD). Our objective was to derive a scoring system to predict 5-year risk of developing CKD in HIV-infected individuals and to estimate difference in risk associated with tenofovir use.

DESIGN

We evaluated time to first occurrence of CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) in 21 590 HIV-infected men from the Veterans Health Administration initiating antiretroviral therapy from 1997 to 2010.

METHODS

We developed a point-based score using multivariable Cox regression models. Median follow-up was 6.3 years, during which 2059 CKD events occurred.

RESULTS

Dominant contributors to the CKD risk score were traditional kidney risk factors (age, glucose, SBP, hypertension, triglycerides, proteinuria); CD4(+) cell count was also a component, but not HIV RNA. The overall 5-year event rate was 7.7% in tenofovir users and 3.8% in nonusers [overall adjusted hazard ratio 2.0, 95% confidence interval (CI) 1.8-2.2]. There was a progressive increase in 5-year CKD risk, ranging from less than 1% (zero points) to 16% (≥9 points) in nonusers of tenofovir, and from 1.4 to 21.4% among tenofovir users. The estimated number-needed-to-harm (NNH) for tenofovir use ranged from 108 for those with zero points to 20 for persons with at least nine points. Among tenofovir users with at least 1 year exposure, NNH ranged from 68 (zero points) to five (≥9 points).

CONCLUSION

The CKD risk score can be used to predict an HIV-infected individual's absolute risk of developing CKD over 5 years and may facilitate clinical decision-making around tenofovir use.