Published: 27-12-2023 11:16 | Updated: 27-12-2023 11:45

Statins tested for severe liver disease

In an unbiased cross-checking of a wide array of health registers, an exciting connection emerged. Could a common and cheap blood lipid lowering drug from the standard repertoire help patients with the liver diseases PSC? This question is now the subject of a clinical trial.

Annika Bergquist, Photo: Stefan Zimmerman

Text: Annika Lund, for the magazine Medicinsk Vetenskap nr 4 2023 / Spotlight on the liver

Last year, 166 livers were transplanted in Sweden. About 25 went to patients with PSC, primary sclerosing cholangitis. It is a rare disease, but one of the most common causes of liver transplantation. 

“This is a disease that affects young people. The average age of onset is between 35 and 40 years, but children are also affected. We recently investigated the fate of 125 children with PSC. One of them needed a transplant before they reached adulthood,” says liver doctor Annika Bergquist, a professor at Karolinska Institutet’s Department of Medicine, Huddinge.

Effective treatment is lacking

In PSC, the bile ducts in the liver become inflamed. As a result, constrictions can occur that prevent bile from flowing out and causing it to remain in the liver. The backed-up bile irritates the liver and creates further inflammation, which leads to the formation of scar tissue. In the long term, this can develop into cirrhosis, which increases the risk of liver cancer. 

Much about the disease, such as why it actually occurs and why some people have more aggressive cases than others, remains unclear. However, there is an evident and close link to inflammatory bowel disease, especially ulcerative colitis. 

Effective treatment is lacking. Today, patients are prescribed a medication that thins the bile fluid so that it can pass through constrictions, which can also be opened with balloon dilation or sometimes a stent. But after about 20 years of illness, one in two patients either dies or needs a transplant. 

A few years ago, Annika Bergquist and her colleagues conducted a register study with the hope of identifying new research questions to pursue. And their fishing expedition was a success. 

Clinical study has been launched

The researchers followed up nearly 3,000 Swedes with PSC via several health registers – the Swedish Prescribed Drug Register, the Swedish Cause of Death Register, the Swedish Cancer Register, and the Swedish Patient Register. A distinct pattern emerged. Patients who took very common lipid-lowering statins had a better prognosis. In that group, deaths and liver transplants occurred half as often as in those who were not prescribed this medication.

“But we can’t conclude that statins have an effect on PSC, based on a register study alone. These patients took the drug for other reasons, perhaps something cardiovascular. So we didn’t get any exact answers about PSC, but it was a good question to pursue,” says Annika Bergquist. 

The researchers have launched a new study funded by a sizeable grant from the Swedish Research Council. 700 patients with PSC will be randomly assigned to receive either 40 mg simvastatin or a placebo over a five-year period. The researchers will investigate differences in mortality, liver transplantation, liver cancer, and varix haemorrhage, a serious complication of liver cirrhosis. So far, just over half of the patients have been included, so it will still be several years before the outcomes of the study are available. 

“At the end of 2023, we will conduct a three-year check-up on the first patient,” says Annika Bergquist.