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.

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

• 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.
  
  

• 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.
  
  

• 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.
  
  

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.
  
  

• 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.
  
  

• 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.
  
  

By Michael Carter

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).