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.”