Curing hepatitis C infection substantially reduces the risk of
developing type 2 diabetes in people with HIV/hepatitis C virus (HCV) co-infection, but does
not reduce the risk of cardiovascular disease, cancers or other
non-AIDS events, a study of people with co-infection treated in Spain between
2000 and 2008 has shown. The findings are published online ahead of
print in the journal Hepatology.
The study also found a trend towards a reduced risk of kidney failure
in those cured of hepatitis C, although the trend did not reach
As well as causing liver damage, hepatitis C infection can lead to
extrahepatic disease, including cryoglobulinemia, chronic kidney disease
and renal failure, diabetes and B-cell non-Hodgkin lymphoma. Hepatitis C
has also been implicated in the development of cardiovascular disease.
Increased blood levels of a protein that can cause inflamed blood vessels
and thicken blood.
Something that has an
effect outside the liver, for example when viral hepatitis affects the kidneys
or causes depression.
type of tumour affecting the lymph nodes.
The presence of pus-forming bacteria in the body.
Curing hepatitis C infection has been shown to reduce the risk of
diabetes, kidney failure and cardiovascular disease in people with mono-infection, but the extrahepatic effects of curing hepatitis C have not been
established in people with HIV and hepatitis C co-infection.
Spanish researchers looked at this question by examining extrahepatic
disease in people with HIV/HCV co-infection treated with interferon and
ribavirin at 19 clinics in Spain between 2000 and 2008. People were
eligible for hepatitis C treatment if they had CD4 cell counts above 200
cells/mm3 and were on stable antiretroviral therapy or were treatment-naïve with no
active injection drug use. Severe concurrent extrahepatic disease
including hypertension, cardiovascular disease, poorly controlled type 2 diabetes and severely reduced kidney function, were also criteria for
The cohort consisted of 1625 people, 75% male, with a median age of
40 years. Baseline liver biopsy was carried out in approximately 70% of
people, of whom 38.6% had bridging fibrosis (F3 or F4), or cirrhosis.
The baseline prevalence of diabetes (2.9%) and chronic renal failure (0.2%) was low.
Most people received pegylated interferon (2a or 2b) (86.5%) rather
than interferon alfa. All received ribavirin. Thirty-eight per cent of
the cohort achieved a sustained virologic response, of which 2.5% were
cured after retreatment.
After completion of treatment, participants were followed for a
median of 5.4 years. 16.2% of non-responders and 11.8% of responders
were lost to follow-up.
The analysis showed very substantial reductions in the risk of death
(HR 0.36, 95% CI 0.24-0.54, p < 0.001), liver-related death (HR 0.13,
95% CI 0.06-0.28, p < 0.001) and new AIDS-defining events (HR 0.37 (95%
CI 0.17-0.79, p = 0.01) in those cured of hepatitis C, in common with a
number of previous studies looking at outcomes after treatment.
During the follow-up period the most frequent new non-liver,
non-AIDS-related events were cancers (6.2%), type 2 diabetes (6%)
cardiovascular event (5.6%), non-AIDS-related infections (sepsis) (5%),
bone events including fractures and osteonecrosis (3.5%) and severe
renal events (2%). Although the frequency of non-liver, non-AIDS events
as a whole was not significantly lower in those who were cured, two
types of events did occur less frequently in people who had been cured
of hepatitis C.
Type 2 diabetes occurred in 3.7% of those cured, compared to 7.5% of
non-responders (p = 0.002), (hazard ratio 0.57, 95% CI 0.35-0.93,
p = 0.024).
Renal events – kidney failure, initiation of dialysis or kidney
transplant – occurred in 0.1% of those cured compared to 2.7% of
non-responders (p = 0.015). The reduction of risk was of borderline
significance (HR 0.42, 95% CI 0.17-1.09, p = 0.074) in multivariate
The analysis also showed a trend towards a higher rate of
cardiovascular events in people who were cured of hepatitis C (HR 1.57,
95% CI 0.99-2.50, p = 0.056).
The researchers say that their findings support an offer of treatment
to anyone with HIV/HCV co-infection who has insulin resistance or type 2 diabetes, regardless of fibrosis stage, and that the decline in the
risk of death, liver-related death, new AIDS-related events and
liver-related events “argue for the prescription of HCV therapy
regardless of liver fibrosis stage in coinfected patients.”