Direct-acting antivirals (DAAs) used in interferon-free regimens are well tolerated, with few side-effects. Overall, the most common side-effects in clinical trials of these drugs were fatigue, headache and gastrointestinal symptoms – usually mild and reported by a minority of participants. Most studies have seen few serious side-effects and few people stopping treatment because of them. Side-effects go away after treatment is completed, and health problems caused by hepatitis C, such as lack of energy and lack of concentration, should also begin to improve.

Although people with HIV and HCV co-infection were prone to worse side-effects from interferon-based therapy, HIV-positive and HIV-negative people appear to tolerate DAAs equally well.

Current guidelines no longer recommend interferon-based therapy, with a few exceptions (see Medications for hepatitis C for more information). Interferon can cause difficult side-effects including fatigue, fever and other flu-like symptoms, muscle or joint pain, nausea or diarrhoea, loss of white blood cells, skin rash, thinning hair and depression.

Some people have a better chance of being cured if they take ribavirin with DAAs. Anaemia is a common side-effect of ribavirin that can lead to fatigue and shortness of breath. Sometimes anaemia can be managed by reducing the ribavirin dose or using erythropoietin, a hormone that stimulates red blood cell production. Anaemia is less frequent when ribavirin treatment lasts for 8 or 12 weeks.

Ribavirin can cause birth defects or miscarriage (pregnancy loss) and must not be taken by women who are pregnant or thinking of becoming pregnant, or by their male partners. Couples in which one or both partners have taken ribavirin should avoid pregnancy and unprotected sex for at least six months after completion of treatment.