Effects of delaying Hepatitis C treatment

Now that better and more effective treatments exist for Hepatitis C (HCV), should all – not just the sickest – patients be eligible for these therapies? David Rowlands’ latest poll examines the issues around treating earlier or waiting.

Deferring antiviral therapy for HCV until a person progresses to advanced liver disease has clear drawbacks, including lower treatment effectiveness and an increased risk of clinical events and death, according to a study of US veterans presented at the European Association for the Study of the Liver (EASL) 50th International Liver Congress in Vienna recently.

Over years, or decades, chronic HCV infection can lead to serious liver disease including cirrhosis, hepatocellular carcinoma (liver cancer), and need for a liver transplant. When the standard of care for HCV was interferon-based therapy, with its long course of treatment, poor tolerability, and only modest cure rate, experts generally recommended delaying treatment until a patient developed advanced disease.


“Treatment is still often limited to the sickest patients, because of the high cost of the new drugs”



Now that much more effective and well-tolerated interferon-free direct-acting antiviral therapy is available, a growing number of providers and advocates say that everyone living with HCV should be eligible. But treatment is still often limited to the sickest patients, because of the high cost of the new drugs.

Treatment-experienced people

People living with HCV who have failed to respond to previous regimens containing direct-acting antivirals may be more difficult to cure, either through drug resistance or because of host factors, such as liver damage. Several studies of interferon-free combinations presented at the International Liver Congress showed that new regimens can be highly effective in this group of patients.

An interferon-free regimen over a 12-week period produced sustained response rates of 83 per cent for people with HCV who had advanced liver cirrhosis and 94 per cent for people who had received liver transplants, with similar cure rates for those with hard-to-treat HCV genotype 3, according to findings from the ALLY-1 trial.

James, 32, from Leicester: “I have previously successfully completed hepatitis C treatment and was re-infected again within the first year. While I feel I did benefit from doing the treatment, I am going to wait for newer, more tolerable treatments with fewer side effects to become available on the NHS.”

Previously untreated people

A 12-week course of the combination of grazoprevir and elbasvir cured 95 per cent of previously untreated people with genotypes 1, 4 or 6 HCV infection, according to results of the C-EDGE trial. The grazoprevir/elbasvir combination pill is due to be submitted for regulatory approval in the US, Europe and other countries shortly, and may be approved by the end of 2015. It will be the third all-oral, interferon-free combination to be marketed exclusively by one company.

Maria, 56, from London: “I have been living with hepatitis C for the past 22 years. I was fortunate to be accepted onto a new trial and successfully completed my treatment within 12 weeks. I was able to continue to work and found that I had minimal & manageable side effects. I feel I now have a higher energy level and able to plan a brighter and clearer future.”

The latest poll investigated this issue, posing the question: ‘Should people living with hepatitis C access hepatitis treatment now? Or should they wait for emerging therapies?’

Out of 142 respondents, 49.9 per cent believed that people should wait for emerging therapies, followed by 33.1 per cent agreeing that people living with HCV should access treatment now. 19 per cent were unsure, which shows the complexity of this subject.

Paul, 51, from London: “I have had hepatitis C for five years and the old treatment didn’t work. Whilst I am fine and my liver is coping well at the moment, I don’t want my health to deteriorate before I am eligible for treatment. Plus I am infectious and, whilst I always make sure I don’t put anyone else at risk, the fact that I could terrifies me. Hepatitis C has more stigma than HIV (I am co-infected) but I would rarely disclose my hepatitis C status. I would just make sure the sex I was having wasn’t risky.”

EASL guidelines

EASL has issued new treatment recommendations. It emphasised the importance of prioritising some groups of people because of a higher risk of liver disease progression. Experts presenting the guidelines said that this would be a reality in many European countries until drug costs came down.


“Treatment is a priority for people with advanced fibrosis or cirrhosis, including people with decompensated cirrhosis, who stand to benefit greatly”



Treatment is a priority for people with advanced fibrosis or cirrhosis, including people with decompensated cirrhosis, who stand to benefit greatly from treatment. Other high-priority groups include people with HIV or hepatitis B virus (HBV) co-infection and people who are awaiting, or have received, a liver transplant.

The following regimens are included in the new guidelines, along with the genotypes for which they are indicated:

Interferon-free regimens:

•Sofosbuvir + ribavirin: genotypes 2 and 3

•Sofosbuvir/ledipasvir +/- ribavirin: genotypes 1, 4, 5, and 6

•Paritaprevir/ritonavir/ombitasvir + dasabuvir +/- ribavirin: genotype 1

•Sofosbuvir + simeprevir +/- ribavirin: genotypes 1 and 4

•Sofosbuvir + daclatasvir +/- ribavirin: all genotypes

•Paritaprevir/ritonavir/ombitasvir +/- ribavirin: genotype 4

Interferon-containing regimens:

•Pegylated interferon alfa-2a + ribavirin + sofosbuvir: all genotypes

•Pegylated interferon alfa-2a + ribavirin + simeprevir: genotypes 1 and 4

The standard duration of interferon-free therapy is generally 12 weeks. Some people with genotype 1 and without cirrhosis can take sofosbuvir/ledipasvir for just eight weeks without ribavirin. People with genotype 1 who have cirrhosis should add ribavirin or extend treatment to 24 weeks. Although HCV subtype 1a is considered harder to treat than 1b, treatment recommendations are generally similar.

Across genotypes, only a few regimens are recommended for people with decompensated cirrhosis: sofosbuvir plus ribavirin (genotype 2 and 3), and sofosbuvir with either ledipasvir (genotypes 1, 4, 5, and 6) or daclatasvir (all genotypes).

Alan, 48, from Glasgow: “I was recently diagnosed with hepatitis C and at present I am unsure about committing to treatment as I am aware I need to change my lifestyle and behavioural patterns first. I do know that I have many treatment options, but I need more support and knowledge of when the best time to complete treatment is, and how best to manage the potential side effects.”

When to treat and liver damage in undiagnosed people

Although European treatment guidelines give priority to people with advanced liver damage, an analysis of people receiving HCV care through the US medical system for military veterans – approximately 187,000 veterans diagnosed with HCV between 1999 and 2010 – found a very strong association between later treatment and an increased risk of clinical illness and death.

This study looked at people treated with pegylated interferon and ribavirin, which is less effective in people with cirrhosis, so it is unsurprising to find that people with cirrhosis had poorer outcomes despite treatment. However, the study also found that people with cirrhosis who were cured still had a poorer long-term prognosis than people who started treatment with less serious liver damage.

Another US study found that approximately one in five people with HCV in that country who do not know of their infection may already have advanced liver damage and be in urgent need of treatment.

Poll data

There were 142 respondents to this poll, between 6 May and 25 May 2015, with data collected via online hosting at www.Design-Redefined.co.uk and social networking sites. Thanks to the community for their input into the poll and this feature.

The next poll examines HIV activism & technology. View the poll and vote here.

About the author:

David Rowlands is the director of Design-Redefined.co.uk, delivering effective healthcare communications to professionals and patients. His key objective is to design, develop and deliver community projects to enable people living with, or affected by, HIV and/or HCV to become better engaged with their treatment and care. Working over a number of media platforms, across the public, private and third sector, he is able to establish a link to these sometimes hard-to-reach communities.

Contact David on email: david@design-redefined.co.uk , Website: www.design-redefined.co.uk , Twitter: @DR_tweetUK

Read about the previous poll:

Depression, alcohol and drug problems: the hidden toll of HIV