Improvements in mood and energy after successful HCV treatments

Untreated, unrecognized or poorly managed mental health issues can be a driver of substance use and can make some people vulnerable to infections such as hepatitis C virus (HCV) and HIV. Once these infections become established, having a chronic viral infection can lead to persistent activation and inflammation of the immune system, which can affect the health of the brain. This effect on the brain occurs because cells of the immune system become activated and inflamed due to the chronic viral infection (in this case HCV) and travel to the brain where they release chemical signals that can trigger inflammation in that organ.

Treatment for HCV and mood

Modern treatments for HCV are called direct-acting antivirals (DAAs). Treatment with DAAs is generally highly effective, with currently approved treatments achieving cure rates greater than 90% in clinics.

 Researchers at a medical centre in the German city of Homburg conducted a study to assess the impact of DAAs on issues such as mood and factors affected by mood, such as physical activity and fatigue. Additionally, the researchers also assessed changes in the blood of the chemical messenger serotonin, a compound that can affect mood.

About serotonin

To manufacture serotonin, the body’s cells start with the amino acid tryptophan, found in many protein-rich foods, and put it through a series of processes. This amino acid is converted by cells into another molecule called 5-HTP (5-hydroxytryptophan), which is then converted into serotonin. Cells, particularly those in the brain, use serotonin and similar molecules to communicate with each other. Some treatments for depression and anxiety are thought to work by affecting serotonin levels.

Study details

Researchers recruited 29 participants with chronic HCV infection—24 received treatment and the remaining five were used for the purposes of comparison. Participants were assessed before, during and after DAA treatment. Researchers took blood samples, surveyed patients with validated health questionnaires and gave them devices to track physical activity.

The average profile of all participants upon entering the study was as follows:

  • 14 men, 15 women
  • age – mid-50s
  • most participants had a moderate degree of liver injury
  • the most common strain of HCV was genotype 1, followed by genotypes 3 and 2

Commonly used combinations of DAAs were as follows:

  • sofosbuvir + ledipasvir (Harvoni)
  • sofosbuvir + ribavirin
  • paritaprevir + ritonavir  + ombitasvir + dasabuvir (Holkira Pak)

Results—Changes in fatigue

Over the course of therapy, researchers found that the degree of fatigue fell significantly in the 24 participants who received DAAs. Furthermore, by the end of treatment, 70% of treated participants reported a lack of fatigue. In contrast, no changes in fatigue occurred among the control group.

Symptoms of depression also improved significantly in treated people but did not change in the control group.

Analyses of blood samples found that levels of the serotonin precursor 5-HTP rose significantly in the blood of DAA-treated participants. An increase in 5-HTP is likely to lead to an increase in serotonin levels.

Overall, the results of this analysis suggest that DAAs have a positive, persistent and likely indirect effect on fatigue and mood. This may come about because DAAs quickly reduce production of HCV and then help eliminate this virus from the body.

—Sean R. Hosein


Hahn D, Stokes CS, Kaiser R, et al. Effects of direct-acting antiviral agents for the treatment of chronic hepatitis c virus infection on serotonin metabolism, depression scores and fatigue. In: Program and abstracts of the International Liver Congress, 19-23 April 2017, Amsterdam, the Netherlands. Poster 253.