June 18, 2018
Hepatitis C virus (HCV) infects the liver, and in many cases this infection becomes established in that organ. Despite this setback, the immune system continually attempts to clear the liver of this infection, and in the process of doing so, it triggers a state of chronic low-level inflammation in the liver. Chronic immune-related inflammation in the liver slowly degrades this organ. Over time, healthy liver tissue is replaced with useless scar tissue. Eventually, most of the liver becomes scarred -- a state called cirrhosis.
Initially, cirrhosis may be symptom free, a situation called compensated cirrhosis. However, over time, symptoms associated with cirrhosis can appear; this is called decompensated cirrhosis. Such symptoms can include the following:
Over the past several years, randomized clinical trials conducted by pharmaceutical companies have shown that all-oral therapy, commonly called direct-acting antivirals (DAAs), can cure many people of HCV. Examples of DAAs used in Canada and other high-income countries include the following:
As a general rule, pharmaceutical companies tend to pick young and relatively healthy adults for trials of their drugs, including DAAs. Although it is true that some participants in clinical trials with DAAs had cirrhosis, the vast majority of people who entered these trials did not have cirrhosis and/or symptoms of cirrhosis. Therefore, now that DAAs have been approved by regulatory authorities, it is important that clinics conduct further clinical trials, called observational studies, to try to understand the ability of these drugs to treat people with cirrhosis.
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Researchers in Canada, Germany, Israel and the U.S. have collaborated in studies of DAAs; this collaboration is called Target. Clinics that are a part of Target prescribe DAAs according to the local standard of care and share their data with other clinics so that large numbers of participants can be assessed and trends can be examined. Target has produced previous analyses that have been useful with older DAAs.
In their most recently released analysis, researchers with Target focused on data collected from people who had cirrhosis and severe liver disease.
More than a decade ago, researchers at the Mayo Clinic in Rochester, New York, developed a scoring system to help predict the risk of death over the 90 days after a person with severe liver injury was admitted to hospital. The scoring system is called MELD (Model for End-stage Liver Disease) and is useful for assessing patients with severe liver disease, including those awaiting a liver transplant. The greater the MELD score, the greater the risk of death within 90 days. To calculate a MELD score, the values of several blood tests are put into an equation.
In the present study, researchers focused on data collected from 488 people. A brief summary of the different genotypes of HCV and the treatments used are as follows:
Genotype-1 (GT-1) -- 352 people
GT-2 -- 32 people
GT-3 -- 85 people
Note that regardless of the genotype, in about 30% of cases, physicians chose to add the broad-spectrum antiviral drug ribavirin to each regimen in the hope of increasing the chances of cure.
The average profile of all participants is as follows:
Overall, 90% of participants were cured regardless of the regimen used.
Factors associated with being cured included the following:
About 73% of participants reported adverse events. In clinical trials, the term adverse events covers a broad range of unfortunate events that occurred, including drug-related side effects and symptoms associated with the underlying disease process. Common adverse events in the present study were as follows:
Since MELD can predict the chances of death in the short-term, it is important to find out if there were any changes with this score after people were cured. However, in the present study, in which most participants had symptoms associated with cirrhosis, MELD scores generally showed only a modest decline, suggesting a small decrease in the risk of death over the short-term after cure. Bear in mind that since most patients had extensive liver disease, it will take years for that organ to recover from HCV-associated injury even though cure was achieved. However, for about 26% of participants, MELD scores decreased by three or more points. Researchers found that people who had a decrease of three or more points in their MELD score were more likely to have the following profile:
Five people died during the study from complications associated with the following:
There was no evidence that DAAs and/or ribavirin caused deaths seen in this study.
Ten other people died after the end of their course of treatment, mostly of cirrhosis-related complications, including liver cancer.
Despite being cured, "patients with advanced liver disease may still be at considerable risk of [developing symptoms associated with cirrhosis] and liver cancer," stated the Target researchers.
Verna EC, Morelli G, Terrault N, et al. Direct-acting antiviral HCV therapy is safe and effective in patients with decompensated cirrhosis: Real-world experience from the HCV-Target cohort. International Liver Congress, 11-15 April 2018, Paris, France. Presentation PS-033.
[Note from TheBodyPRO: This article was originally published by CATIE on June 15, 2018. We have cross-posted it with their permission.]
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