European guidelines on management of mental health for people with hepatitis C published

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European investigators have developed a consensus statement on hepatitis C and mental health. Published in the online edition of the Journal of Hepatology, the wide-ranging document assesses evidence concerning the effect of hepatitis C infection and its treatment on the brain and mental health. It also reviews the evidence for the prevalence and risk factors of psychiatric problems in hepatitis C-infected people and makes recommendations regarding the treatment and care of patients with mental health problems.

An estimated 170 million individuals are infected with hepatitis C worldwide. Chronic infection can lead to permanent liver damage and death. There is a high prevalence of psychiatric problems in people with hepatitis C. Some evidence suggests that the infection itself may be a cause, possibly due to its effect on the central nervous system. It is also well known that standard hepatitis C therapy with pegylated interferon and ribavirin can have psychiatric side-effects. These can include depression, fatigue, insomnia and cognitive disturbances.

Given these concerns, the European Liver Patients Association convened a meeting of European investigators in 2011 to develop a consensus statement based on current knowledge of mental health problems during hepatitis C infection and treatment and the treatment of psychiatric-related disorders.



A mental health problem causing long-lasting low mood that interferes with everyday life.


Tiredness, often severe (exhaustion).


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. 


The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.


The general term for the body’s response to injury, including injury by an infection. The acute phase (with fever, swollen glands, sore throat, headaches, etc.) is a sign that the immune system has been triggered by a signal announcing the infection. But chronic (or persisting) inflammation, even at low grade, is problematic, as it is associated in the long term to many conditions such as heart disease or cancer. The best treatment of HIV-inflammation is antiretroviral therapy.

Their recommendations are based on a grading of the quality of current evidence, and cover six broad areas.

Hepatitis C and the brain

  • Psychiatric problems are significantly more prevalent in hepatitis C-infected people.
  • Mental health problems are associated with an increased risk of acquiring hepatitis C.
  • Symptoms such as depression, fatigue and cognitive impairment could be due to the effect of hepatitis C on brain chemistry or inflammation.
  • Hepatitis C infection is associated with stigma, anxiety and reduced quality of life, leading to high levels of psychosocial distress.
  • There is evidence that hepatitis C alters the metabolism of the central nervous system.
  • Recent research shows that the infection can enter and replicate within the central nervous system.

Neuropsychiatric side-effects of pegylated interferon

  • Hepatitis C therapy based on pegylated interferon is associated with increased incidence of depression, fatigue, sleep disturbances, fatigue, irritability, cognitive disturbances and thoughts of suicide.
  • Therapy is less frequently associated with mania, confusion, psychotic syndromes, attempted suicide and aggressive or compulsive behaviour.
  • Symptoms including fatigue, sleep disturbances and decreased appetite appear almost immediately after treatment is started.
  • Depression and cognitive problems usually emerge between weeks 4 and 24 of therapy and are at their most intense between weeks 8 and 16.
  • Therapy based on pegylated interferon is associated with changes in neurobiology.
  • Changes to the serotonin and dopamine metabolism may be an important cause of depression and fatigue.
  • Alterations in brain chemistry and toxicities may be contributing towards cognitive changes.

Risk factors for depression or suicide associated with pegylated interferon

  • Depression during a previous course of therapy based on pegylated interferon.
  • Depression before treatment was started.
  • Sleep problems during therapy.
  • The emergence soon after starting therapy of sleep problems or loss of appetite.
  • Stress or lack of social support before initiating treatment.
  • Genetic factors.
  • Biomarkers of inflammation.
  • A previous psychiatric history may be a risk factor for suicide.

Psychosocial management

The following are recommended before treatment:

  • Information should be sought regarding psychiatric history, drug use, employment status and sources of social support.
  • An interdisciplinary approach involving hepatologists, psychiatrists and addiction specialists is recommended for people with underlying mental health and/or substance abuse issues.
  • People should be provided with information about possible neuropsychiatric side-effects.

During and after treatment:

  • Mood changes should be monitored at regular intervals during therapy and until week 12 after its cessation.
  • More intensive monitoring is recommended for individuals with possible mental health problems or substance abuse issues.
  • People with drug addiction can achieve good treatment outcomes.
  • People with pre-existing psychiatric disorders can achieve good treatment outcomes.
  • Therapy should not be considered for people with uncontrolled mental health or addiction problems.
  • All patients with psychiatric or drug use issues should receive interdisciplinary care.

Management, acute treatment and prevention of psychiatric problems associated with pegylated interferon

  • Depression responds to therapy with antidepressants.
  • When selecting an antidepressant, consideration should be given to possible drug interactions.
  • Antidepressants should be continued for at least twelve weeks after hepatitis C treatment has been completed.
  • Early treatment of sleep disturbances is recommended.
  • Antidepressants reduce the incidence and severity of interferon-associated depression, regardless of prior psychiatric history.
  • Prophylactic antidepressant therapy should be considered for people with a prior history of depression.
  • Escitalopram is recommended as the firstline antidepressant because of the low risk of interactions.

New antivirals and pegylated interferon

  • There are potential interactions between the new hepatitis C protease inhibitors and some sleeping tablets, antidepressants, antipsychotics, methadone and antiepileptics, but more information is needed.

Schaefer M et al. Hepatitis C infection, antiviral treatment and mental health: a European expert consensus statement. J Hepatol, advance online publication, August 2012 (abstract available).