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Why Depression is Likely With Hepatitis C

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Physicians are finding an increasing correlation with HCV infection and clinical depression. Learn about the four possible mechanisms linking depression with Hepatitis C, as well as the role standard combination therapy may play in this relationship.

As the most common blood borne viral infection today, the Hepatitis C virus (HCV) is a major cause of chronic liver disease and affects an estimated 180 million people worldwide. For many living with HCV, the standard therapy of peginterferon-alfa and ribavirin is either not an option or it was unsuccessful. Whether an HCV-infected person has not attempted standard therapy or is a non-responder, physicians are finding an increasing correlation with HCV infection and clinical depression. Being aware of depression’s prevalence among this population and its potential mechanisms will encourage both patients and their physicians to take depression seriously.

Defining Depression

According to the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), major depressive disorder is characterized by a period of depressed mood or anhedonia (inability to experience pleasure from normally pleasurable life events such as eating, exercise, social or sexual interaction) occurring for at least two consecutive weeks. Depressed mood or anhedonia must also be accompanied by at least four of the following:

  • Overwhelming sadness or emptiness
  • Lack of interest or pleasure in daily activities
  • Appetite or weight changes
  • Disturbed sleep patterns
  • Changes in psychomotor activity
  • Fatigue or loss of energy
  • Feelings of guilt or worthlessness
  • Difficulty focusing, concentrating or making decisions
  • Recurrent thoughts of death or suicidal ideation

A result of inconsistent measures of depression, calculating the actual prevalence of depression among patients with chronic HCV infection is challenging. Nevertheless, most researchers and physicians agree that the prevalence of depressive disorders is significantly higher among HCV-infected patients compared with the general population. According to the DSM-IV criteria, reported prevalence rates for major depressive disorder are higher in those with HCV:

  • Ranging from 24 to 70 percent with chronic Hepatitis C infection
  • Ranging from 6 to 10 percent in the general population

HCV Treatment

Hepatitis C’s current standard of treatment consists of combination therapy with peginterferon-alfa and ribavirin for 24 or 48 weeks depending on viral genotype. Although the treatment response rates are favorable for those able to complete this therapy, many must abandon the treatment protocol due to combination therapy’s severe side effects. Some studies indicate that chemically-induced depression occurs in approximately 20 to 40 percent of treated patients. Administering physicians have observed that depression associated with HCV therapy reduces the likelihood of eliminating the virus with peginterferon-alfa and ribavirin, due to patient non-compliance or even premature discontinuation.

Possible Mechanisms

The various factors contributing to major depressive disorder makes it difficult to establish a causative relationship between HCV infection and depression. The origins of depression with Hepatitis C are most likely a combination of physiological characteristics of the virus, emotional and physical health of the individual, the extent of a person’s social support network, personal beliefs and available treatment options. Following are four potential mechanisms connecting chronic HCV infection and depression:

  1. Pre-Existing Condition – This theory suggests that having a psychiatric disorder, such as depression or posttraumatic stress disorder, can lead to high-risk behaviors increasing the probability for HCV infection, such as intravenous drug use or unprotected sexual practices. According to this premise, HCV itself is not the causative agent for depression, but there is a high prevalence of depression in individuals who engage in risky behaviors. Several studies have found higher incidences of drug use and unsafe sexual practices among patients with major depressive disorder or other depressive symptoms.
  2. Psychological Impact of HCV – This theory suggests that depression related to HCV infection is due to the psychological burden and distress associated with this chronic disease. Foster and colleagues demonstrated that in a sample of HCV-infected patients without cirrhosis, quality of life scores were reduced, particularly regarding mental health and physical function, when compared with a control group. Many health experts are recognizing that chronic Hepatitis C virus infection alone leads to physical symptoms capable of reducing a person’s quality of life, the springboard for depression.
  3. Biological Result of HCV – This theory describes the potential for the Hepatitis C virus to negatively affect the central nervous system bringing about depression. Although not directly proven, this hypothesis is supported by studies demonstrating that HCV directly causes fatigue and other neuro-cognitive symptoms. Adair and colleagues used gene expression analysis to evaluate gene expression in HCV-infected patients and a control group. The researchers found a difference in the expression of 29 genes, including those involved in brain oxidative and energy metabolism. These findings support a biological basis for the link between HCV infection and depression. Additionally, Hepatitis C viral particles noted to cause chemical changes that could initiate depressive symptoms have been found in the central nervous system.
  4. Psycho-Spiritual Perception – Best-selling author and motivational speaker, Esther Hicks, describes depression as a location on one extreme edge of an emotional scale. On one end of this scale, good feelings are likened to the perception of freedom; on the other end bad feelings are likened to the perception of bondage. Bondage, otherwise felt as lack of freedom or control, embodies the empty sensation of depression. According to this psycho-spiritual theory, Hepatitis C is often associated with depression, because many affected feel that their ability to recover from this illness is beyond their control. Such feelings of hopelessness in those with Hepatitis C may occur when those affected:
    • Are informed their disease is incurable
    • Feel doubtful about ridding themselves of Hepatitis C
    • Experience severe side effects from standard therapy, causing the perception that their condition is worsening – further confirming a loss of control over their health

By accumulating hopefulness about a Hepatitis C diagnosis, a person will naturally progress on the emotional scale away from fear, and thus away from depression.

Patients and their physicians must be aware of the simultaneous presentation of HCV and depression, the role combination therapy may play in this relationship and the four possible mechanisms linking depression with Hepatitis C. Armed with this knowledge, we can be proactive in addressing major depressive disorder as affiliated with chronic Hepatitis C infection.


http://clinicaloptions.com, Risks and Mechanisms of Depression in HCV, Michael R. Krauss, MD, PhD, Depression Associated With HCV Infection and Its Therapy: Impact on Patient Management, Clinical Care Options, LLC, March 2007.

http://jac.oxfordjournals.org, Interferon-induced depression in chronic hepatitis C, Y. Horsmans, Journal of Antimicrobial Chemotherapy, September 2006.

www.abraham-hicks.com, It’s All About Vibrational Relativity, Abraham-Hicks Publications, 2007.

www.natap.org, Chronic Hepatitis C, Depression and Interferon, Journal of Hepatology, June 2005.

www.psychiatrictimes.com, Depression as Co-Pilot: Clinical Implications of Hepatitis C and Interferon/Ribavirin Treatment, James A. Bourgeois, MD, OD, Lorenzo Rossaro, MD, and Robert D. Canning, PhD, Psychiatric Times, April 2005.


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