Digestive and Liver Disease 37 (2005) 564–565
Depression and liver diseases M. Germana Orr`u a , Carmine M. Pariante b,∗ b
a Psychiatric Cinic, University of Cagliari, Italy Section of Clinical Neuropharmacology, Institute of Psychiatry, King’s College London, 1 Windsor Walk, Denmark Hill, London SE5 8AF, UK
Available online 23 May 2005 See related article, on pages 593–600
Clinical experience tells us that hepatic diseases are often associated with psychiatric symptoms, but accurate measures of this association are lacking. Moreover, of all hepatic diseases, only chronic hepatitis C is frequently studied in terms of psychiatric morbidity, because this disease is a common and growing problem; however, psychiatric symptoms can characterise all liver diseases, especially if associated with cirrhosis. Therefore, the paper by Bianchi et al. , describing patients with liver cirrhosis related to alcohol, hepatitis virus B or C (HCV), autoimmunity, cholestasis or metabolic abnormalities, is an important contribution to the literature. Neurocognitive abnormalities, anxiety and, above all, depression, are psychiatric symptoms frequently associated with chronic viral hepatitis [2,3]. The percentage of depression reported in these patients is up to 58% . A high percentage of patients with hepatitis C show clinically relevant scores for depression , and the prevalence rate of depression is much higher in HCV patients than in healthy controls [5,6]. Moreover, depression has been reported to be sufficiently severe to require psychopharmacological treatment in 20% of chronic HCV patients . Of course, many patients with a HCV infection are intravenous drug users. However, Johnson et al.  found that depressive symptoms are similar in drug users with and without hepatitis C. Other authors found the same result, that the mode of acquisition of the virus does not have a relevant influence on developing depression [3,5]. Interestingly, several studies in patients with chronic viral hepatitis indicate that disease severity and the histological grade of liver damage have no significant influence ∗
Corresponding author. Tel.: +44 20 7848 0807; fax: +44 20 7848 0051. E-mail address: [email protected]
on the emotional state [3,5,7]. The paper by Bianchi et al.  suggests that the relationship between liver damage and emotional state may become evident in patients with cirrhosis. Depression is an important problem in patients with cirrhosis. Patients with cirrhosis and depression are significantly more likely to die while awaiting transplantation than patient with cirrhosis and without depression . Interestingly, Singh et al.  have shown that a significantly higher number of patients with depression had cirrhosis associated with viral hepatitis. This highlights the role of viral infection in the genesis of depression in patients with liver cirrhosis. The paper by Bianchi et al.  does not specifically address this issue; however, they identify another potentially important risk factor for depression in patients with cirrhosis: active alcohol drinking. The aetiology of depression in patients with liver diseases is unknown. Neuropsychological impairment has been well documented in patients with cirrhosis and end-stage liver diseases. These deficits, mostly evident as abnormalities in cognitive functions, are also co-related with the presence of depression. Moreover, these deficits are also found in up to 50% of non-cirrhotic patients . In fact, mild cognitive impairments may be evident even before the development of cirrhosis . In patients with hepatitis C, a mild mood disturbance could be part of the neuropsychological syndrome associated with the infection . Indeed, Forton et al.  found brain abnormalities in patients with hepatitis C infection, using proton magnetic resonance spectroscopy. They suggest that these abnormalities form the basis of a general neuropsychological syndrome that also includes depression. Thus, it is possible that fatigue and depression, in patients with chronic
1590-8658/$30 © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2005.04.003
M.G. Orr`u, C.M. Pariante / Digestive and Liver Disease 37 (2005) 564–565
hepatitis C, could be due to a neuropathogenic effect of the virus [12,13]. Even less is known about the role of psychosocial factors in the course of chronic liver diseases. First, personality and chronic psychosocial stress seems to be related to the severity of chronic viral hepatitis C . Second, patients with recently diagnosed hepatitis C have significantly lower levels of depression than patients with a longer time-interval since the initial diagnosis ; therefore, the longer the time the patients have known about the diagnosis, the worse is their emotional state. Third, depression may be reactive, secondary to the patients’ perception of a “failing health status”, as rightly suggested by the paper by Bianchi et al. . In their paper, there is a close association between global Beck Depression Inventory (a measure of depression), its somatic subscale (indicating symptoms like sleep disorders, fatigue, loss of appetite), and liver function. Fourth, the presence of some specific somatic symptoms seems particularly important: fatigue is a frequent and disabling component, which impairs quality of life in these patients and is associated with depression . This may be particularly true in patients with chronic viral hepatitis, where the severity of depressive symptoms has been found to be associated with fatigue, functional disability and somatizations . Finally, patients with chronic viral hepatitis also have a strong perception of stigma, which can also contribute to depression . Future studies should look at these more complex components of psychological well-being. A final, important point—as underlined in the article by Bianchi et al. , there are many psychiatric patients with liver diseases, and many cirrhotic patients with psychiatric problems. Unfortunately, the presence of psychiatric symptoms could be a barrier to receive proper medical care. For example, patients with chronic viral hepatitis and psychiatric problems are often discriminated in their access to interferonalpha because of the unfounded concern that these patients may have more severe psychiatric adverse effects during interferon alpha therapy. We have found that interferon-alpha is a safe drug for these patients [17–19]. Nguyen et al.  have recently described that only a small percentage of patients with chronic viral hepatitis and psychiatric problems is unable to start or successfully complete the antiviral therapy because of worsening of the psychiatric symptoms or of relapse of the drug or alcohol use. A close liaison between medical teams and psychiatric services is, in our opinion, very important to correctly approach these problems. Indeed, the percentage of patients who receive the correct antiviral therapy seems to be lower in the centres that do not offer co-ordinated access to both liver specialists and psychiatrists . An integrated approach is the best answer to this kind of problem; a team of hepatologists interested in psychiatry, as Bianchi et al., is a very good start. Conﬂict of interest statement None declared.
References  Bianchi G, Marchesini G, Nicolino F, Graziani R, Sgarbi D, Loguercio C, et al. Psychological status and depression in patients with liver cirrhosis. Dig Liver Dis 2005;37:593–600.  Forton DM, Thomas HC, Murphy CA, Allsop JM, Foster GR, Main J, et al. Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. Hepatology 2002;35:433–9.  Goulding C, O’Connel P, Murray F. Prevalence of fibromyalgia, anxiety and depression in chronic hepatitis C virus infection: relationship to RT-PCR status and mode of acquisition. Eur J Gastroenterol Hepatol 2001;13:507–11.  Dieperink E, Willenbring M, Ho SB. Neuropsychiatric symptoms associated with hepatitis C and Interferon alpha: a review. Am J Psychiatry 2000;157:867–76.  Kraus MR, Csef ASH, Scheurlen M, Faller H. Emotional state, coping styles and somatic variables in patients with chronic hepatitis C. Psychosomatics 2000;4:377–84.  Lee D, Jamal H, Regenstein F, Perrillo R. Morbidity of chronic hepatitis C as seen in a tertiary care medical center. Dig Dis Sci 1997;42:186–91.  Kunkel EJ, Kim JS, Hann HW, Oyesanmi O, Menefee LA, Field HL, et al. Depression in Korean immigrants with hepatitis B and related liver disease. Psychosomatics 2000;41:472–80.  Johnson ME, Fisher DG, Fenaugthy A, Theno SA. Hepatitis C virus and depression in drug users. Am J Gastroenterol 1998;93:785–9.  Singh N, Gayowsky T, Wagener MM, Marino IR. Depression in patients with cirrhosis. impact on outcome. Dig Dis Sci 1997;42:1421–7.  Hilsabeck RC, Perry W, Hassanein TI. Neuropsychological impairment in patients with chronic hepatitis C. Hepatology 2002;35:440–6.  Forton DM, Allsop JM, Main J, Foster GR, Thomas HC, TaylorRobinson SD. Evidence for a cerebral effect of the hepatitis C virus. Lancet 2001;358:38–9.  Kramer L, Bauer E, Funk G, Hofer H, Jessner W, Steindl-Munda P, et al. Subclinical impairment of brain function in chronic hepatitis C infection. J Hepatol 2002;37:349–54.  Weissenborn K, Krause J, Bokemeyer M, Hecker H, Schuler A, Ennen JC, et al. Hepatitis C virus infection affects the brain—evidence from psychometric studies and magnetic resonance spectroscopy. J Hepatol 2004;41:845–51.  Nagano J, Nagase S, Sudo N, Kubo C. Psychosocial stress, personality and the severity of chronic hepatitis C. Psychosomatics 2004;45:100–6.  Huet PM, Deslauriers J, Tran A, faucher C, Charbonneau J. Impact of fatigue on the quality of life of patients with primary biliary cirrhosis. Am J Gastroenterol 2000;95:760–7.  Dwigth MM, Kowdley KV, Russo JE, Ciechanowsky PS, Larson AM, Katon WJ. Depression, fatigue and functional disability in patients with chronic hepatitis C. J Psychosom Res 2000;49:311–7.  Pariante CM, Orr`u MG, Baita A, Farci MG, Carpiniello B. Treatment with IFN alfa in patients with Chroni Hepatitis and mood or anxiety disorders. Lancet 1999;354:131–2.  Pariante CM, Landau S, Carpiniello B. Interferon alpha-induced neuropsychiatric adverse effect in patients with psychiatric diagnosis: a prospective, controlled study. N Engl J Med 2002;347:148– 9.  Orr`u MG, Baita A, Sitzia R, Costa A, Muntoni E, Landau S, et al. Interferon alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective observational study. Epidemiol Psichiatr Soc, in press.  Nguyen HA, Miller AI, Dieperink E, Willenbring ML, Tetrick LL, Durfee JM, et al. Spectrum of disease in US veterans patients with hepatitis C. Am J Gastroenterol 2002;97:1813–20.