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EASL 2014: Sustained Response to Treatment Reduces Fatigue in Hepatitis C Patients


Curative treatment that eliminates hepatitis C virus (HCV) from the body can reduce central fatigue, one of the most problematic symptoms associated with chronic hepatitis C, according to research presented at the EASL Liver International Liver Congressthis month 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 anemia, which can lead to fatigue by reducing the blood's ability to carry oxygen. The advent of direct-acting antiviral agents enables people with hepatitis C to either take interferon or ribavirin for a shorter duration or to avoid them altogether.

Zobair Younossi and colleagues with Inova Health System in Virginia evaluated changes in fatigue among hepatitis C patients 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 patients 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 anemia (a hemoglobin decrease of 2 g/dL or more).

Fatigue was assessed using 3 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 (4 items) and peripheral fatigue (9 items).

  • After achieving SVR12, participants had significant improvement in fatigue compared to their pre-treatment scores using all questionnaires.
  • SF-36 vitality scale: 26.9% improvement;
  • CLDQ-HCV activity-energy domain: 10.7% improvement;
  • FACIT-F fatigue scale: 19.8% improvement.
  • After successful treatment the proportion of patients who scored below the general population norm decreased using all questionnaires:
  • SF-36 vitality scale: from 32.7% to 27.6%;
  • CLDQ-HCV activity-energy domain: from 47.9% to 35.4%;
  • FACIT-F fatigue scale: from 43.4% to 34.6%.
  • All items in the 3 questionnaires related to central fatigue showed improvement, while only 2 items related to peripheral fatigue did so.

"Sustained virologic responseis 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."



Z Younossi, M Stepanova, L Gerber, et al. Improvement of Central Fatigue is Associated with Sustained Virologic Response (SVR) Following Sofosbuvir-Containing Regimens. 49th European Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract P717.