statins decreases the risk of progression to liver cirrhosis in people with HIV/hepatitis C virus (HCV) co-infection, investigators from the United
States report in AIDS. The protective
effect of statins was most evident in people with normal liver function, with each 30% increase in the amount of time taking statins reducing the risk of
cirrhosis by approximately a third. The research also showed that several
other metabolic risk factors were association with progression to cirrhosis, especially
in people with poorer liver function.
“To our knowledge,
this is the largest study of HIV/HCV co-infected individuals to examine the
effect of statin drugs on cirrhosis development,” comment the authors. “We have
demonstrated that statin drug use in patients with HIV/HCV co-infection and
normal liver function decreased the risk of cirrhosis, particularly among those
with ALT < 40 IU/L. Among patients with ALT > 40 IU/L metabolic
risk factors including low-HDL and diabetes were significantly associated with
development of cirrhosis.”
fifth of all people with HIV have co-infection with HCV. Liver disease is a
leading cause of serious illness and death in this group of people. Statins have an
anti-inflammatory effect. Investigators from the United States Department of
Veterans Affairs designed a retrospective study to see if statin therapy
reduced the risk of progression to cirrhosis in people with co-infection. Their
analysis also examined the effect of other metabolic and HIV-related risk
factors on the development of liver disease.
Approximately 6000 people with co-infection who entered care between 1999 and 2010 were included in
the study. In addition to statin use, data were collected on metabolic risk
factors, including obesity, diabetes, hypertension and low HDL cholesterol.
Information was also obtained on age at HIV diagnosis, use of antiretroviral therapy (ART), CD4 count
and percentage of time with an undetectable viral load. Individuals were
stratified according to their liver function (ALT below/above 40 IU/L).
Almost all (99%) participants
were men, two-thirds were black and mean age at the time of HIV diagnosis was
45 years. The mean duration of follow-up was 6.2 years and by the end of
follow-up 2265 people had developed cirrhosis, an incidence of 6 per 100
Most people (83%)
received ART and 53% had a CD4 cell count of at least 350 cells/mm3. People who developed cirrhosis were significantly less likely than
those who remained free of cirrhosis to have received ART (80% vs. 86%) and to have a
CD4 count of 350 cells/mm3 or above (49% vs. 59%). People with
cirrhosis also had a significantly shorter period of time with viral
suppression than those without cirrhosis (20% vs. 29%).
factors were highly prevalent. Over 50% of the cohort had hypertension or low HDL
cholesterol and 16% had diabetes. Few received statin therapy, with
the treatment prescribed to 13% and 21% of people with and without cirrhosis,
In people with
ALT < 40 IU/L, every 1% of time on statins was associated with
decreased risk of cirrhosis (aHR = 0.98; 95% CI, 0.97-0.99). For every
30% of time taking statins during the follow-up period, participants in
the cohort with ALT < 40 IU/L had a 32% reduction in the risk of cirrhosis.
For individuals with
higher ALT values, statin therapy did not significantly reduce the risk of
progression to cirrhosis. For people with an ALT above 40 IU/L risk factors
for the development of cirrhosis included diabetes (aHR = 1.15; 95% CI,
1.01-1.31) and low HDL cholesterol (aHR = 1.3; 95% CI, 1.2-1.44). Hypertension
was associated with a non-significant increase of progression to cirrhosis in
both ALT groups. Obesity was protective against the development of cirrhosis
among people with higher ALTs (aHR = 0.85; 95% CI, 0.76-0.95).
People aged over
50 years with an ALT < 40 IU/L had a more than twofold increase in
the risk of cirrhosis (aHR = 2.5; 95% CI, 1.54-1.8). Higher number of
co-morbidities was also a risk factor for cirrhosis progression in people
with normal liver function (aHR = 3.25; 95% CI, 2.3-4.5), and alcohol use was
associated with liver disease progression in individuals with higher ALT values
(aHR = 1.15; 95% CI, 1.04-1.26).
A CD4 count below
200 cells/mm3 was associated with progression to cirrhosis,
regardless of liver function, increasing the risk of progression twofold. People whose viral load was undetectable for at least 80% of the time
significantly reduced their risk of progression to cirrhosis (aHR = 0.72 for
both ALT groups).
acknowledge a number of limitations in their research, including its
retrospective design and the overwhelmingly male population, meaning that its
results may not apply to more diverse patient groups.
demonstrated that statin use in an HIV/HCV co-infected population with minimal
liver dysfunction was associated with a reduced risk of progression to advanced
liver disease,” conclude the investigators. “Statin use may be an important,
and cost-effective adjunct in the care of HIV/HCV co-infected patients.”