People with hepatitis and liver cirrhosis were
significantly less likely to progress to decompensated disease and less likely
to die if they used statins to control blood cholesterol, according to an
analysis of US veterans presented at the Digestive Disease Week meeting this
week in Washington, DC, and at the European Association for the Study of the
Liver (EASL) 50th International Liver Congress last month in Vienna, Austria.
Another recent study found that statins were associated with better response to
hepatitis C treatment and lower risk of liver cancer.
Over years or decades, chronic hepatitis C virus (HCV)
infection can lead to severe liver disease including cirrhosis (when scar
tissue replaces functional liver cells and blocks blood circulation) and
hepatocellular carcinoma (a type of liver cancer). Some people eventually
experience decompensation when the liver can no longer carry out its vital
functions, resulting in symptoms such as ascites (abdominal fluid
accumulation), bleeding varices (swollen veins) in the stomach or oesophagus
and hepatic encephalopathy (brain impairment).
Arpan
Mohanty of Yale School of Medicine and colleagues looked at the effects of
statin use on decompensation and mortality in people with hepatitis C and
compensated cirrhosis.
Glossary
- albumin
A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).
- ascites
An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis.
- compensated cirrhosis
The earlier stage of
cirrhosis, during which the liver is damaged but still able to perform most of
its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.
- encephalopathy
-
A disease or infection affecting the brain.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
- varices
Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.
Statins are used to lower blood cholesterol levels. They have been shown
to prevent cardiovascular disease and reduce the risk of heart attack, stroke
and death. Statins also have anti-inflammatory effects and some research has
found them to be associated with reduced liver fibrosis progression and lower
risk of liver cancer.
Studies have also shown that statins can decrease portal pressure –
blood pressure in the veins that carry blood from the stomach and intestines
through the liver – in people with cirrhosis and to improve survival in people with bleeding varices, the researchers noted as background. However,
the long-term effects of statins on decompensation and mortality in people
with compensated cirrhosis are unknown.
Mohanty's team retrospectively
analysed data from the Veterans Affairs (VA) HCV Clinical Case Registry from January
1996 through December 2009. Out of more than 45,000 HIV-negative VA patients
with hepatitis C and compensated cirrhosis, they identified a subset of 1323
eligible statin users seen at outpatient clinics. From within this group, a
total of 685 statin users were matched with up to five people with hepatitis C and cirrhosis who did not use statins (n = 2062).
Almost all matched
participants were men, half were white, 21% were black and the median age was
56 years. People with HIV or hepatitis B were excluded, as were liver
transplant recipients and people recently diagnosed with HCV infection,
cirrhosis or liver cancer. Nearly a third had coronary artery disease, more
that 80% had high blood pressure, about half had diabetes and two-thirds were
smokers. The median duration of statin use was 2.8 years. Propensity scores for
matching took into account demographics, co-morbid conditions and variables
associated with statin prescription such as blood lipid levels and cardiovascular
disease.
Decompensation was defined as having one inpatient or
two outpatient diagnostic codes for ascites, bleeding oesophageal varices or
spontaneous bacterial peritonitis (internal infection). Statistical analyses
were adjusted for patient age, body mass index, albumin level, FIB-4 score
(used to estimate extent of fibrosis) and MELD score (an indicator of liver
disease severity).
Over a follow-up period of more than two years, statin
use was associated with a lower risk of both liver decompensation and death
compared to non-use (hazard ratio [HR] 0.55 and 0.56, respectively, or about a
45% risk reduction). These associations persisted after adjusting for liver
disease variables.
"In compensated HCV cirrhosis, statin users have
a significantly lower incidence of decompensation and better overall survival
compared to statin non-users," the researchers concluded. "Risk of decompensation
and death was reduced by over 40%."
Mohanty
noted that only 43% of patients with total cholesterol
>200 mg/dl and 65% of those with LDL 'bad' cholesterol >160 mg/dl
received statins in this cohort. These high cholesterol levels were traditionally
considered indicators for statin therapy, though the latest guidelines from the
National Institute for Health and Care Excellence and the American
Heart Association and American College of Cardiology base
statin recommendations on overall cardiovascular risk rather than specific
cholesterol thresholds.
"Statin use is low in patients with
cirrhosis, even in those with a high cardiovascular risk," Mohanty said.
Until randomised controlled trials are conducted, statins cannot be widely
recommended for all people with hepatitis C and cirrhosis, she added, but for patients
who otherwise require statins, "their use should not be avoided."