Study advances search for novel liver cirrhosis treatments
Liver disease – which includes cirrhosis of the liver – is a leading cause of morbidity and mortality in Europe. It also tends to affect a younger population than other chronic conditions such as cardiovascular disease and lung cancer. “Liver disease is caused by two key issues – alcohol and metabolic factors such as diabetes, obesity and metabolic syndrome,” explains LIVERHOPE project member Elisa Pose from the Hospital Clínic of Barcelona – IDIBAPS in Spain. “It can take years for clinical symptoms to appear.”
Unmet late-stage cirrhosis clinical need
In later stages of the disease when mortality rates are very high, there are very few effective treatments available. The EU-funded LIVERHOPE project led by Pere Ginès (Hospital Clínic of Barcelona – IDIBAPS) sought to address this clinical need. This was achieved through the trial of an innovative new therapy, designed to improve the prognosis of late-stage cirrhosis patients. The trial built on previous research which suggested that combining rifaximin – an antibiotic – and simvastatin – a lipid-lowering drug – could be effective in treating the condition. “Rifaximin is already used for cirrhosis patients, while there has been growing scientific interest in the possible beneficial effects of simvastatin,” says Pose. To fully understand the efficacy of this treatment, the LIVERHOPE project team conducted two randomised double-blind trials. Five EU countries were involved, along with 14 university hospitals and 237 volunteer patients. “This trial was carried out at the highest levels of clinical practice,” notes Pose.
Analysing the combined effect on patients
The most important finding was that the trial was unable to definitively show a positive effect from combining the two drugs on late-stage cirrhosis patients. “The end point we used was ambitious,” explains Pose. “We wanted to prevent severe complications of the disease but couldn’t show these beneficial effects on the patients treated.” Given that previous scientific evidence had suggested the drugs could be effective, Pose says it was necessary to conduct a trial of this depth and quality. “We needed to know whether combining these drugs would have a beneficial effect.” Furthermore, it is possible that the cohort of patients used were too ill to respond to medicine. Results might have been more positive if patients with less advanced stages of the disease had been treated. “There are two similar international clinical trials under way at the moment, with similar cohorts of patients,” remarks Pose. “It will be really interesting to see if the negative results are confirmed or not.”
Next steps towards treating late-stage cirrhosis
The LIVERHOPE project was a necessary step forward in the search for effective therapies to treat late-stage cirrhosis. While it is probable that simvastatin can have a beneficial impact, researchers will need to redefine the disease stage at which patients are treated. “There are other promising treatments currently being tested,” adds Pose. “One is the application of albumin, a protein that is produced in the liver. Recent studies have suggested that this may be beneficial for patients, though further investigation is needed.” Another interesting line of research is faecal microbiome transplantation. This has been used to treat different chronic diseases. “Pilot preliminary studies have shown beneficial effects in treating cirrhosis,” says Pose. “Our research team will conduct a trial in the next few years, to see if it might help to slow disease progression.”
Keywords
LIVERHOPE, cirrhosis, liver, cancer, disease, cardiovascular, rifaximin
