Could Statins Help Treat Cirrhosis?

Nearly 5 million adults in the United States are estimated to have advanced liver disease, including cirrhosis, a chronic, late-stage form of all liver diseases. Although significant lifestyle changes and current treatments may help slow the progression of the disease, there is no cure for cirrhosis. More effective treatments are needed to help slow progression to decompensated cirrhosis, the stage where the liver is unable to perform its essential functions.

Tamar Taddei, MD, professor of medicine (digestive diseases), is investigating whether statins—a common, inexpensive medication—may be used to help treat cirrhosis and slow progression to decompensated cirrhosis. She is the co-primary investigator of the SACRED study, a Phase III, prospective clinical trial that enrolled veterans at 11 VA centers nationwide who are at risk of decompensation. Taddei and her colleagues are studying whether statin use is associated with a decrease in the risk of death or hepatic decompensation.

In a Q&A, Taddei discusses current understanding of how statins function and her motivations and challenges in pursuing this line of research.

There has been a longstanding—and inaccurate—view that statins increase the risk of injury to people with chronic liver disease. We now know liver damage from statins is rare and the benefits of taking a statin often outweigh the risks for most people. We do avoid using statins in patients with decompensated cirrhosis, as they are more likely to develop drug-induced liver injury.

In 2015, my colleague Guadalupe Garcia-Tsao, MD, professor of medicine (digestive diseases), and colleagues published one of the first observational studies examining how statins affect the liver. Their study found that people with hepatitis C-related compensated cirrhosis who were on statins had 40% lower risk of cirrhosis decompensation and death.

This study dovetailed with basic science research that came out around the same time showing statins cause vascular relaxation in the liver and other beneficial effects.

Since then, limited clinical research has been conducted on how statins specifically affect people with cirrhosis, making this area ripe for further investigation.

Although there is still much we don’t know about how statins work, we do know they have a variety of effects on the human body beyond lowering cholesterol.

A healthy liver is like a sponge with a bed of capillaries that filters blood coming from the intestines after food is digested. This blood carries not only nutrients but also other substances such as toxins, drugs, and products from gut bacteria that need to be cleaned or processed.

In an individual with cirrhosis, chronic damage leads to scarring around this capillary network, causing the liver to become hard like a rock rather than a sponge. Because of the resistance caused by the scarring, blood flow is impeded and diverted to other blood vessels outside the liver, which become enlarged and dilated. When these enlarged veins (called varices) rupture, it can be life threatening.

Research has indicated that statins can reduce inflammation and scarring and improve vascular health by relaxing the endothelial cells that line capillaries. These are plausible biological explanations for why we think statins may reduce complications of cirrhosis.

One of the main challenges is that most people with compensated cirrhosis are already on a statin for high cholesterol, which often is accompanied by other common conditions like diabetes, high blood pressure, and excess weight. This complicates efforts to find a sample of people to study who are not already on a statin for a different indication than cirrhosis. This is going to be a challenge for anyone who wants to study the use of statins in people with cirrhosis.

I hope that as more people explore this topic, we will have more patient data to help definitively determine whether patients with cirrhosis should receive a statin and which type of statin is most effective in this population. This will require team science across institutions to ensure an adequate sample size for statistically and clinically significant conclusions.

We can surmount challenges by careful study design, rigorous data analysis, and collaboration. These clinical studies may also yield important findings that can be taken back to the laboratory to further our understanding of the biology of liver disease. We would all welcome an effective, well-tolerated, and inexpensive approach to improving liver disease.

Digestive Diseases, one of 10 sections in the Yale Department of Internal Medicine, is committed to advancing the science and practice of gastroenterology and hepatology through extensive laboratory and clinical research, comprehensive training for future leaders in liver and gastrointestinal disorders, and the delivery of state-of-the-art patient care. To learn more, visit Digestive Diseases.