Mustafa ÇELİK, NAZLIM AKTUĞ DEMİR, ŞUA SÜMER, LÜTFİ SALTUK DEMİR

Kronik hepatit B hastalarında sosyodemografik özellikler, antiviral tedavi ve nekroinflamatuar aktivitenin depresyon ve anksiyete ile ilişkisi

Amaç: Kronik hepatit hastalarında depresyon ve anksiyete gibi psikiyatrik bozuklukların sağlıklı kişilerde olduğundan daha sık görüldüğü bilinmektedir. Bu artış kronik bir hastalığa sahip olmanın getirdiği ruhsal zorlanma ile ilişkili olabileceği gibi, karaciğerdeki nekroinflamatuar aktivite, antiviral ilaçlar ve interferon tedavisinin yan etkisi veya hepatit virüslerinin merkezi sinir sistemine doğrudan etkisi gibi birden çok etkenle de ilişkili olabilir. Bu çalışmada kronik hepatit B hastalarında anksiyete ve depresyon ile ilişkili olabilecek çeşitli etkenlerin değerlendirilmesi amaç- landı. Yöntem: Bu çalışma 195 kronik hepatit B hastası üzerinde yapıldı. Hastalarla aynı psikiyatri uzmanı tarafından yapılan klinik görüşmeler sonunda, araştırıcılar tarafından hazırlanan Sosyodemografik Bilgi Formu, Hamilton Anksiyete Değerlendirme Ölçeği (HADÖ) ve Hamilton Depresyon Derecelendirme Ölçeği (HDDÖ) dolduruldu. Amerikan Karaciğer Hastalıkları Çalışmaları Birliği ölçütlerine göre biyopsi endikasyonu konulan hastalara iğne biyopsisi yapıldı. Biyopsi materyalinin değerlendirilmesinde Knodell Histolojik Aktivite Endeksi kullanıldı. Hastaların serumundan HBV DNA ve ALT düzeyleri ölçüldü. Bulgular: Çalışmaya alınan kişilerin 119u erkek, 76sı kadındı. HADÖ puanı ortalaması 7.3±6.2, HDDÖ puanı ortalaması 8.8±6.6 olarak bulundu. Kadınlarda hem HADÖ hem de HDDÖ puanları erkeklerden yüksek bulundu. Kronik hepatit B için aile öyküsü olanlarda HADÖ, eşlik eden medikal hastalık varlığında ise hem HADÖ hem de HDDÖ puanı olmayanlardan yüksek saptandı. Alanin aminotransferaz (ALT), HBV DNA düzeyleri ve karaciğer biyopsisindeki fibrozis ile HADÖ ve HDDÖ puanı arasında bir ilişki saptanmadı. Pegile-interferon tedavisi alanlarla, oral antiviral tedavi kullananlar arasında Hamilton depresyon ve anksiyete puanları açısından fark saptanmadı. Sonuç: Kronik hepatitlerle depresyon ve anksiyete gibi psikiyatrik bozukluklar arasındaki ilişki birden fazla koşuldan etkilenmektedir. Çalışmamızın sonuçları hastanın etnik kökeni, ailede hastalık öyküsü ve ek tıbbi hastalık varlığının nekroinflamatuar aktivitenin veya hücresel hasarın şiddeti veya kullanılan tedavilerden daha etkili olduğunu düşündürmektedir. (Anadolu Psikiyatri Derg 2015; 16(6):405-412)

Association of sociodemographical features, antiviral treatment, and necroinflammatory activity with depression and anxiety in chronic hepatitis B patients

Objective: Psychiatric disorders like depression and anxiety are known to be more prevalent in patients with chronic hepatitis B than healthy individuals. This increased prevalence may be due to multiple factors such as psychological distress associated with having a chronic disease, necroinflammatory activity in liver, side effects of treatment with antiviral agents or interferons, and/or direct effect of hepatitis viruses on central nervous system. Purpose of this study was to evaluate several risk factors that may be associated with anxiety and depression in patients with chronic hepatitis B. Methods: This study included 195 chronic hepatitis B patients. A psychiatrist made clinical interviews with the patients and filled Sociodemographic Data Form, Hamilton Anxiety Rating Scale (HARS), and Hamilton Depression Rating Scale (HDRS). Needle biopsies were performed to 175 patients who met biopsy criteria of American Association for the Study of Liver Diseases. Knodell Histological Activity Index was used to evaluate biopsy materials. HBV DNA and ALT levels were measured from patients sera. Findings: In the study sample, 119 patients were males and 76 were females. Mean HARS score was 7.3±6.2 and mean HDRS score was 8.8±6.6. Both HARS and HDRS scores were higher in females than males. HARS score was higher in patients with a family history of chronic hepatitis and both HARS and HDRS scores were higher in patients with comorbid medical illness. Alanine aminotransferase, HBV DNA levels, and level of fibrosis in liver biopsy didnt affect HARS or HDRS scores. Also, there wasnt a difference in HARS or HDRS scores according to patients usage of pegylated interferon, or oral antiviral therapy. Conclusion: Multiple factors affect the relation between chronic hepatitis and psychiatric disorders like anxiety and depression. Results of our study suggest that female sex, presence of a family history for chronic hepatitis B, comorbidity of other medical diseases, and ethnic origin affect more than the level of necroinflammatory activity and cellular damage in the liver or antiviral treatments.

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1. WHO. Chronic Hepatitis B. www.who.int/ entity/mediacentre/factsheets/fs204/en/ - 31k.
2. Myers RP, Tainturier MH, Ratziu V, Piton A, Thibault V, Imbert-Bismut F, et al. Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B. J Hepatol 2003; 39(2):222-230.
3. Evon DM, Verma A, Dougherty KA, Batey B, Russo M, Zacks S, et al. High deferral rates and poorer treatment outcomes for HCV patients with psychiatric and substance use comorbidities. Dig Dis Sci 2007; 52(11):3251-3258.
4. El-Serag HB, Kunik M, Richardson P, Rabeneck L. Psychiatric disorders among veterans with hepatitis C infection. Gastroenterology 2002; 123(2):476-482.
5. Keskin G, Gümüs AB, Orgun F. Quality of life, depression, and anxiety among hepatitis B patients. Gastroenterol Nurs 2013; 36(5):346-356.
6. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver biopsy. AASLD position paper. Hepatology 2009; 49:1017-1044.
7. Kanwal F, Hays RD, Kilbourne AM, Dulai GS, Gralnek IM. Are physician derived disease severity indices associated with health-related quality of life in patients with end-stage liver disease? Am J Gastroenterol 2004; 99:1726-1732.
8. Younossi ZM, Boparai N, McCormick M, Price LL, Guyatt G. Assessment of utilities and healthrelated quality of life in patients with chronic liver disease. Am J Gastroenterol 2001; 96:579-583.
9. 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.
10. Kraus MR, Csef H, Scheurlen M, Faller H. Emotional state, coping styles and somatic variables in patients with chronic hepatitis C. Psychosomatics 2000; 41:377-384.
11. Colagreco JP, Bailey DE, Fitzpatrick JJ, Musil CM, Afdhal NH, Lai M. Watchful waiting: role of disease progression on uncertainty and depressive symptoms in patients with chronic hepatitis C. J Viral Hepat 2014; 21(10):727-733.
12. Afşar A, Özdemir NF, Sezer S, Haberal M. Quality of life is not related with liver disease severity but with anemia, malnutrition, and depression in HCV infected hemodialysis patients. Hemodial Int 2009; 13(1):62-71.
13. Rifflet H, Vuillemin E, Oberti F, Duverger P, Lainé P, Garré JB, et al. Suicidal impulses in patients with chronic viral hepatitis C during or after therapy with interferon alpha. Gastroenterol Clin Biol 1998; 22:353-357.
14. Gohier B, Goeb JL, Rannou-Dubas K, Fouchard I, Calès P, Garré JB. Hepatitis C, alpha interferon, anxiety and depression disorders: a prospective study of 71 patients. World J Biol Psychiatry 2003; 4:115-118.
15. Marcellin P, Lau GK, Zeuzem S, Heathcote EJ, Pockros PJ, Reddy KR, et al. Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2a. Liver Int 2008; 28:477-485.
16. Ozkan M, Corapçioglu A, Balcioglu I, Ertekin E, Khan S, Ozdemir S, et al. Psychiatric morbidity and its effect on the quality of life of patients with chronic hepatitis B and hepatitis C. Int J Psychiatry Med 2006; 36:283-297.
17. Lee K, Otgonsuren M, Younoszai Z, Mir HM, Younossi ZM. Association of chronic liver disease with depression: a population-based study. Psychosomatics 2013; 54(1):52-59.
18. AlHuthail YR. Comparison of the prevalence of psychiatric co-morbidities in hepatitis C patients and hepatitis b patients in Saudi Arabia. Saudi J Gastroenterol 2013; 19(4):165-171.
19. Ferenci P, Staufer K. Depression in chronic hepatitis: the virus, the drug, or the ethnic background? Liver Int 2008; 28:429-431.
20. Yu ML1, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, et al. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut 2007; 56:553-559.
21. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiat 1960; 23:56.
22. Akdemir A, Türkçapar MH, Orsel SD, Demirergi N, Dag I, Ozbay MH. Reliability and validity of the Turkish version of the Hamilton Depression Rating Scale. Compr Psychiatry 2001; 42:161-165.
23. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32:50-55.
24. Yazici K, Demir B, Tanriverdi N, Karaağaoğlu E, Yolac P. Hamilton Anksiyete Değerlendirme Ölçe- ği, değerlendiriciler arası güvenirlik ve geçerlik çalışması. Turk Psikiyatri Derg 1998; 9(2):114- 117.
25. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1:431-435.
26. Özdemir S, Yaluğ İ, Mert A, Aker T. Psikiyatrik bakış açısıyla kronik hepatitler. Anadolu Psikiyatri Derg 2008; 9:253-260.
27. Horikawa N, Yamazaki T, Izumi N, Uchihara M. Incidence and clinical course of major depression in patients with chronic hepatitis type C undergoing interferon-alpha therapy: a prospective study. Gen Hosp Psychiatry 2003; 25:34-38.
28. Leutscher PD, Lagging M, Buhl MR, Pedersen C, Norkrans G, Langeland N, et al. Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C. Hepatology 2010; 52:430- 435.
29. Hauser P, Khosla J, Aurora H, Laurin J, Kling MA, Hill J, et al. A prospective study of the incidence and open-label treatment of interferon induced major depressive disorder in patients with hepatitis C. Mol Psychiatry 2002; 7:942-947.
30. Raison CL, Borisov AS, Broadwell SD, Capuron L, Woolwine BJ, Jacobson IM, et al. Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry 2005; 66(1):41-48.
31. Fontana RJ, Hussain KB, Schwartz SM, Moyer CA, Su GL, Lok AS. Emotional distress in chronic hepatitis C patients not receiving antiviral therapy. J Hepatol 2002; 36(3):401-407.
32. Hussain KB, Fontana RJ, Moyer CA, Su GL, Sneed-Pee N, Lok AS. Comorbid illness is an important determinant of health-related quality of life in patients with chronic hepatitis C. Am J Gastroenterol 2001; 96(9):2737-2744.
33. Krueger C, Hawkins K, Wong S, Enns MW, Minuk G, Rempel JD. Persistent pro-inflammatory cytokines following the initiation of pegylated IFN therapy in hepatitis C infection is associated with treatment-induced depression. J Viral Hepat 2011; 18:e284-291.
34. Singh N, Gayowski T, Wagener MM, Marino IR. Vulnerability to psychologic distress and depression in patients with end-stage liver disease due to hepatitis C virus. Clin Transplant 1997; 11:406- 411.
35. Kunkel EJ, Kim JS, Hann HW, Oyesanmi O, Menefee LA, Field HL, et al. Depression in Korean immigrants with hepatitis B and related liver diseases. Psychosomatics 2000; 41(6):472-480.
36. Renault PF, Hoofnagle JH, Park Y, Mullen KD, Peters M, Jones DB, et al. Psychiatric complication of long-term alpha therapy. Arch Intern Med 1987; 147:1577-1580.
37. Yumru M, Sırmatel F, Vırıt O, Savaş E, Savaş HA, Herken H. İnterferon tedavisi alan ve almayan hepatit C hastalarında anksiyete ve depresyon düzeyleri. Klinik Psikofarmakoloji Bülteni 2006; 16:155-159.
38. Uluğ M, Can Uluğ N. Kronik hepatitli hastalarda interferon tedavisi öncesi psikiyatrik değerlendirme yapılması: Bir olgu sunumu. Anatol J Investig 2010; 4(2):125-127.
39. Loftis JM, Hauser P. The phenomenology and treatment of interferon-induced depression. J Affect Disord 2004; 82(2):175-190.
40. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347(13):975-982.
41. Alian S, Masoudzadeh A, Khoddad T, Dadashian A, Mohammadpour RA. Depression in hepatitis B and C, and its correlation with hepatitis drugs consumption (Interfron/Lamivodin/Ribaverin). Iran J Psychiatry Behav Sci 2013; 7:24-29.
42. Weinstein AA, Kallman Price J, Stepanova M, Poms LW, Fang Y, Moon J, et al. Depression in patients with nonalcoholic fatty liver disease and chronic viral hepatitis B and C. Psychosomatics 2011; 52:127-132.