Drugs that have been hailed as a cure for a debilitating and sometimes fatal liver disease – but have threatened to break the health budgets of most countries because of their cost – have not been proven to have any effect, according to a new review.

The startling conclusion came from the respected and independent Cochrane Collaboration, which has assessed all the drug company trials of the breakthrough hepatitis C treatments.

Hepatitis C is a viral infection that causes chronic liver disease and can lead to death from cirrhosis and cancer. Previous treatments were not very effective and had side effects that many patients could not tolerate.

The new direct-acting antiviral drugs (DAAs) were hailed as little short of a miracle because they cleared the hepatitis C virus from the blood within 12 weeks, but the price, at about £30,000 per patient, has caused huge concern around the world. Experts from the World Health Organisation (WHO) said last June that no country in the world could afford to treat all those who needed the drugs.

The WHO estimated that treating all those infected would eat up a large part of the drugs budget in every country, from 10.5% in the Netherlands to 190% in Poland. The UK would have to spend a third of its drugs budget on the medicines. About 160 million people are infected and there are about 700,000 deaths a year globally as a result of hepatitis C.

But the Cochrane Collaboration, whose expert group on liver disease is based in Denmark, has published a review of all the randomised controlled trials conducted by the manufacturers in order to get the drugs licensed. It finds that the drugs may clear the virus from the blood, but there is no evidence that they prevent harm from disease or save lives.

Janus Christian Jakobsen, chief physician at a clinical trial unit in Copenhagen and deputy co-ordinating editor of the Cochrane Hepato-Biliary Group, said: “It is never possible to show that something does not work, but there is no evidence [that they do]. Our results indicate [the drugs] may have no clinical effect.”

The effect of the drugs has been measured in the trials by the amount of virus remaining in the blood stream after treatment. But, the review says, that does not mean there is no virus lingering in the body. There is evidence, they say, that in the sickest people treated with the drugs (stage 3 or 4), the virus can return and cause end-stage liver disease.

The trials collected very little evidence about the impact of the drugs in countering the symptoms of hepatitis C disease and there were few deaths either among those taking the drugs or those taking a placebo, says the review.

The reviewers included all the drug trials they could find, published and unpublished – in total, 138 trials randomising a total of 25,232 participants. All the trials were funded by the manufacturers of the drugs and therefore “at high risk of bias,” they say.



“The lack of valid evidence and the possibility of potentially harming people with chronic hepatitis ought to be considered before treating people with hepatitis C with DAAs,” they conclude.

AbbVie, one of the companies making the drugs, commented: “We do not recognise the conclusions of this report, as both controlled trials and real world experience contradict its findings. A cure in [hepatitis C] is defined as undetectable virus in the blood 12 weeks after completing treatment and, in the UK, fewer than 1% of people treated with AbbVie’s therapy did not achieve this.”

Gilead, which manufactures the drugs, said that the primary goal of treatment was to “cure the infection by eradicating the hepatitis C virus”. Nice, the National Institute for Health and Care Excellence, had said they were value for money because the patient becomes less infectious and is likely to require fewer NHS visits. A report from Public Health England in 2015 showed there had been an 8% decrease in end-stage liver disease and a decrease in liver transplants following introduction of the drugs.

The Cochrane reviewers say, however, that they have included all controlled trials in their review. “Sustained virological response is a surrogate outcome,” added Jakobsen. “From a patient perspective, it does not matter if virus cannot be detected in the blood if DAAs do not improve survival or lead to fewer hepatitis C complications. Furthermore, the validity of this surrogate outcome has been questioned before our review was published.”

A second company making the drugs, Bristol Myers Squibb, said it had no comment to make about the review.

