Statins reduce risk of progression to cirrhosis in people with HIV/HCV co-infection

Treatment with statins decreases the risk of progression to liver cirrhosis in people with HIV and 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 a 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 associated 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.”

Approximately a fifth of all people with HIV have co-infection with HCV. Liver disease is a leading cause of serious illness and death in people with HIV/HCV co-infection. 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.

Glossary

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

alanine aminotransferase (ALT)

An enzyme found primarily in the liver. Alanine aminotransferase may be measured as part of a liver function test. Abnormally high blood levels of ALT are a sign of liver inflammation or damage from infection or drugs.

statin

Drug used to lower cholesterol (blood fats).

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

diabetes

A group of diseases characterized by high levels of blood sugar (glucose). Type 1 diabetes occurs when the body fails to produce insulin, which is a hormone that regulates blood sugar. Type 2 diabetes occurs when the body either does not produce enough insulin or does not use insulin normally (insulin resistance). Common symptoms of diabetes include frequent urination, unusual thirst and extreme hunger. Some antiretroviral drugs may increase the risk of type 2 diabetes.

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 person-years.

Most people (83%) received ART and 53% had a CD4 cell count of at least 350 cells/mm3. Those who developed cirrhosis were significantly less likely than people 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%).

Metabolic risk 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, respectively.

In people with ALT < 40 IU/L, every 1% of time on statins was associated with a 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 people with higher ALT values, statin therapy did not significantly reduce the risk of progression to cirrhosis. For those 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).

Participants 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. Participants 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).

The authors 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.

“This study 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.”

References

Oliver NT et al. Statin drugs decrease progression to cirrhosis in HIV/HCV co-infected individuals. AIDS, doi: 10.1097/QAD.0000000000001219 (2016).