Insulin resistance is associated with the progression of liver fibrosis in people co-infected with HIV and hepatitis C, Canadian researchers report in the online edition of AIDS.
Earlier research has shown that hepatitis C virus (HCV) infection is associated with higher insulin levels and insulin resistance. The presence of insulin resistance is associated with poorer responses to hepatitis C therapy in mono-infected patients.
However, it is unclear if the progression of insulin resistance is associated with the progression of liver fibrosis in co-infected patients.
To answer this question, investigators from the Canadian Co-infection Cohort Study (CCC) designed a prospective study involving 158 co-infected patients. None of these individuals had diabetes and all received care between 2003 and 2010.
Insulin levels were monitored at baseline and a series of analyses controlling for potential confounders were performed to see if this or any other factor was associated with the progression of liver fibrosis.
A HOMA-IR (fasting insulin x fasting glucose) score of 2 or above was used as the definition of insulin resistance. An APRI (100 x AST/upper limit of normal/platelet count) score of 1.5 or above was considered to indicate the presence of significant fibrosis.
Most of the patients (63%) were men, their median age was 45 years, approximately a quarter had a history of recent injecting drug use and 89% were taking HIV therapy.
On entry to the study, 56% of patients had insulin resistance. After adjusting for potential confounders, the investigators found that the only factor associated with insulin resistance at this time was a body mass index (BMI) of 25 or above (AOR = 3.66; 95% CI, 1.70-7.92). The authors were concerned by such a high prevalence of insulin resistance and believe that “routine screening for insulin resistance among co-infected patients may be warranted”.
There was no significant evidence at baseline that insulin resistance was associated with the presence of liver fibrosis.
A total of 15 patients (18%) patients developed significant fibrosis during a median of 1.4 years of follow-up.
The rate of disease progression was significantly higher in the participants with insulin resistance at baseline (16.32 per 100 person-years) than those without insulin resistance (7.95 per 100 person-years).
A HOMA-IR score of 2 or above at baseline was associated with the progression of fibrosis (AHR = 7.72; 95% CI, 2.55-23.36). “We found insulin resistance was strongly associated with the development of hepatitis fibrosis,” write the authors.
The presence of fibrosis at baseline was the only other significant factor (AHR = 7.92; 95% CI, 1.94-32.42).
The investigators were uncertain why co-infected patients appear to be vulnerable to insulin resistance, but offer the inflammatory effects of hepatitis C infection as a possible explanation. They add, “whether HIV directly plays a role remains unclear”.
However, the investigators stress that BMI was the most significant risk factor for baseline insulin resistance and that this is potentially modifiable through changes in diet and with exercise. They therefore conclude: “Interventional studies to manage modifiable risk factors for insulin resistance and evaluate the role of pharmacotherapy in modifying the course of liver disease progression and improving HCV treatment outcomes in HIV-HCV co-infected persons are needed.”
Hull MW et al. Insulin resistance is associated with progression to hepatitis fibrosis in a cohort of HIV/HCV co-infected patients. AIDS 26, online edition. DOI: 10.1097/QAD.0b013e32835612ce, 2012.