Sustained response to treatment reduces fatigue in hepatitis C patients

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Curative treatment that eliminates hepatitis C virus (HCV) from the body can reduce central fatigue, one of the most concerning symptoms associated with chronic hepatitis C, according to research presented at the 49th annual meeting of the European Association for the Study of the Liver (EASL), held recently in London. 

Fatigue is a common and debilitating symptom for many people with hepatitis C. Central fatigue refers to weakness originating in the central nervous system (the brain and spinal cord), as opposed to peripheral or physical fatigue that originates in the muscles.

Fatigue is also a common side-effect of treatment with interferon and ribavirin. Ribavirin often causes anaemia, which can lead to fatigue by reducing the blood's capacity to carry oxygen. New direct-acting antiviral agents allow people with hepatitis C to either take interferon or ribavirin for a shorter duration or to avoid them altogether.



Tiredness, often severe (exhaustion).



A shortage or change in the size or function of red blood cells. These cells carry oxygen to organs of the body. Symptoms can include shortness of breath, fatigue and lack of concentration.

sustained virological response (SVR)

The continued, long-term suppression of a virus as a result of treatment. In hepatitis C, refers to undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 12 or 24 weeks after ending treatment and is considered to be a cure (SVR12 or SVR24).

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 


A drug that acts against a virus or viruses.

Zobair Younossi and colleagues with Inova Health System in Virginia evaluated changes in fatigue among people with hepatitis C treated and cured with sofosbuvir, either with pegylated interferon and ribavirin in the NEUTRINO trial (genotypes 1, 4, 5 and 6) or with ribavirin alone in the FUSION trial (genotypes 2 and 3).

The analysis included 413 people who achieved sustained virological response, or undetectable HCV RNA at 12 weeks after finishing treatment (SVR12). About 60% were men, most were white, the mean age was 52 years and 18% had liver cirrhosis. At baseline, 12% of study participants reported fatigue, 18% reported anxiety and 24% each reported insomnia and depression. During treatment 87% developed anaemia (a haemoglobin decrease of 2 g/dL or more).

Fatigue was assessed using three validated questionnaires: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV) and Short Form-36 (SF-36). The researchers focused on items related to both central fatigue (four items) and peripheral fatigue (nine items).

After achieving sustained response, participants reported significant improvement in fatigue compared to their pre-treatment scores using all questionnaires: average 26.9% improvement on the SF-36 vitality scale, 19.8% on the FACIT-F fatigue scale and 10.7% on CLDQ-HCV activity-energy domain. All items in the questionnaires related to central fatigue showed improvement, while only two items related to peripheral fatigue did so.

In addition, after successful treatment the proportion of patients who scored below the general population norm decreased using all questionnaires: from 32.7% to 27.6% on the SF-36 vitality scale, from 43.4% to 34.6% on the FACIT-F fatigue scale and from 47.9% to 35.4% on the CLDQ-HCV activity-energy domain.

"Sustained virologic response is associated with improvement of fatigue," the researchers concluded. "Central fatigue is the type of fatigue primarily affected by HCV clearance. Longer follow-up may be needed to show any potential improvement in peripheral fatigue."


Younossi Z et al. Improvement of central fatigue is associated with sustained virologic response (SVR) following sofosbuvir-containing regimens. 49th Annual Meeting of the European Association for the Study of the Liver (EASL), abstract P717, London, 2014.