Treatment with pegylated interferon and
ribavirin is associated with lasting improvements in insulin resistance among
HIV-positive people co-infected with hepatitis C, investigators report in the
online edition of Clinical Infectious
Hepatitis C therapy was also associated
with transient falls in levels of cholesterol.
“Our data demonstrate that treatment with
pegylated interferon and ribavirin can significantly affect lipid profile and
that there may be a modest improvement in insulin resistance,” comment the
authors. However, they are unclear about the significance of their findings and
call for further research.
Standard therapy for hepatitis C consists
of pegylated interferon and ribavirin. A successful response to this treatment
has been associated with increases in lipid levels in hepatitis C-monoinfected
Infection with hepatitis C has also been
associated with the development of diabetes. Insulin resistance (which occurs when the impact of insulin secretion on blood sugar levels is diminished) is a precursor to the development of type 2 diabetes. There is some evidence that successful treatment of of hepatitis C monoinfection is associated with a reduced risk of diabetes and impaired fasting glucose.
However, the impact of treatment on lipid
levels and insulin resistance in HIV/hepatitis C-co-infected patients is
US investigators therefore designed a
prospective study involving 182 co-infected patients.Their primary aim was to evaluate the effect of a prolonged course of pegylated interferon and ribavirin on fibrosis progression in prior non-responders to this regimen.
Their secondary aim was to evaluate the impact of
hepatitis C therapy on total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol,
triglycerides and insulin resistance (HOMA-IR above 2.5).
The participants had a median age of 48 years,
most (81%) were men and they were of mixed ethnicity. Median baseline hepatitis
C viral load was 6.6 log10. The majority of patients (82%) had
genotype-1 infection. HIV therapy was widely used (84%). Approximately
three-quarters of patients had an undetectable HIV viral load and median CD4
cell count was 508 cells/mm3.
Baseline lipid profiles were as follows:
Total cholesterol, 171 mg/dl.
HDL cholesterol, 42 mg/dl.
Triglycerides, 139 mg/dl.
LDL cholesterol, 95 mg/dl
(among the 92% of patients with triglycerides below 400 mg/dl).
The median HOMA-IR was 3.3 and 62% of
participants were classified as having insulin resistance.
There was a significant relationship
between hepatitis C viral load and triglyceride levels (p < 0.0001).
A quarter of participants achieved a sustained
virological response. Higher LDL cholesterol was associated with an increased
chance of achieving a therapeutic response (OR = 1.17 each 10 mg/dl increase;
95% CI, 1.03-1.32).
An early virological response to treatment
(undetectable or 2 log10 reduction in hepatitis C viral load at week
twelve) was achieved by 57% of patients. These individuals received an extended
course of treatment with pegylated interferon and ribavirin lasting 72 weeks.
Significant falls in total cholesterol,
HDL cholesterol and LDL cholesterol were observed by week 16 of treatment (all
p < 0.001) and these persisted through to week 64 (p < 0.001). However,
each of these measurements had returned to near their baseline levels 24 weeks
after the completion of treatment.
Triglyceride levels had increased
significantly by week 16 (+ 30 mg/dl, p < 0.001) and there was a further
modest increase by week 64 (+ 23 mg/dl, p = 0.07). However, within six months
of the end of therapy, triglycerides had returned to baseline levels.
“The significance and mechanism of these
changes is not clear,” comment the investigators. However, they note that some
research suggests that hepatitis C “may alter the expression profile of lipid
Modest improvements were seen in HOMA-IR
values at weeks 16 and 24. Six months after the completion of treatment, there
was an overall significant decline in HOMA-IR (- 0.7; p = 0.02).
“Values of HOMA-IR showed a gradual modest
decline while on treatment which persisted at 24 weeks after completion of
treatment, suggesting an added benefit of therapy in…co-infected persons,”
write the researchers. “Whether this improvement eventually translates into a
decrease in incidence of overt diabetes mellitus, or improvement in glycemic
controls in those who are already diabetic, requires further investigation.”