A Review of Sleep Disturbance in Hepatitis C Sanjeev Sockalingam, MD, FRCPC,*w Susan E. Abbey, MD, FRCPC,*w z Fahad Alosaimi, MBBS, SSC-Psych,wyJ and Marta Novak, MD,*wz Abstract: Sleep disturbances occur in up to 60% of patients with chronic hepatitis C (CHC) and is often interrelated with comorbid psychiatric disorders. Moreover, neuropsychiatric complications of interferon-a during CHC treatment can manifest as sleep problems. Newly diagnosed sleep disturbance occurs in up to 60% and 30% of untreated CHC patients and patients undergoing interferon-a therapy, respectively. However, the presentation of insomnia in patients with CHC is influenced by significant psychiatric comorbi- dity, such as depression, and medical conditions, such as anemia and hypothyroidism. Therefore, prompt recognition using screen- ing tools and exclusion of comorbid conditions contributing sleep pathology can enhance treatment outcomes. Owing to the paucity of studies, treatment recommendations for sleep disorders in CHC patients are derived from recommendations from general sleep disorder treatment guidelines. Further research is needed to eluci- date the efficacy of pharmacological and nonpharmacological treatments of sleep disorders in CHC patients. Key Words: hepatitis C, sleep, liver diseases (J Clin Gastroenterol 2010;44:38–45) H epatitis C virus infection is a growing public health concern, with approximately 170 million people chroni- cally infected worldwide. 1 The existing literature on the neuropsychiatric comorbidity in chronic hepatitis C (CHC) infected patients has identified depression, fatigue, and anxiety as common comorbid syndromes. However, a paucity of studies have assessed sleep problems in CHC patients. This is surprising given that sleep problems are commonly reported by CHC patients and there is an established relationship between sleep disorders and quality of life in the medically ill patient populations. 2 Sleep problems are often interrelated with other comor- bid conditions in CHC patients. For example, insomnia during CHC may exacerbate chronic fatigue, which can occur in up to 75% of CHC patients and reduce health-related quality of life. 3 Major depression occurs in approximately 30% to 50% of CHC patients and further complicates the differential diagnosis of sleep problems. 4,5 Moreover, approximately 20% of CHC patients will develop cirrhosis over 20 years which may culminate in hepatic encephalopathy, which can manifest as sleep-wake reversal. Furthermore, treatment of CHC with interferon-alpha (IFNa) has been associated with 2 distinct syndromes: (i) a depression-specific syndrome consisting of depressed mood, cognitive symptoms, anxiety, and suicidal ideation; and (ii) a neurovegetative syndrome consisting of reduced energy, fatigue, anorexia, and sleep disturbance (also termed ‘‘sickness behavior’’). 6 Therefore, prompt recognition and management of sleep problems during CHC treatment may facilitate improved IFNa treatment adherence and treatment outcomes. The purpose of this review is to summarize the published information about the prevalence rate and risk factors for sleep disorders in patients with CHC, both pre- IFNa and during IFNa treatment. A summary of potential pathoetiological factors will be discussed in the context of hepatitis C. Finally, we will provide an approach to the diagnosis and management of sleep disturbance in CHC patients. MATERIALS AND METHODS Using PubMed, we searched for all English language articles published between January 1985 and September 2008 to identify studies on sleep disorders in CHC. We used combined the following search terms as follows: ‘‘hepatitis C’’ or ‘‘chronic hepatitis’’ or ‘‘liver cirrhosis’’ or ‘‘inter- feron-alpha’’ and ‘‘sleep’’ or ‘‘insomnia.’’ We supplemented our literature search with manual reviews of references listed in the identified articles. A total of 17 articles were identified, however, we did not find any sleep disorders treatment studies specific to CHC patients. Given the dearth of literature in this area, this review will provide an overview on sleep disorders in CHC patients, diagnosis and general treatment options based upon guidelines on treatment of sleep disorder in the general population. Identified studies will be cited in the relevant sections and supplemented with data extracted from patients with sleep disorders and other liver pathology where applicable. Most Common Sleep Disorders Sleep disorders include largely heterogenous conditions and syndromes and can be classified as primary sleep disorders and secondary sleep disorders. The most detailed definition of sleep disorders can be found in the International Classification of Sleep Disorders, 2nd edition. 7 The International Classifica- tion of Sleep Disorders, 2nd edition classifies sleep disorders in 8 major categories: insomnias, sleep-related breathing dis- orders, hypersomnias of central origin, circadian rhythm sleep disorders, parasomnias, sleep-related movement disorders, Copyright r 2009 by Lippincott Williams & Wilkins From the *Department of Psychiatry, University of Toronto; wDivision of Medical, Illness and Mental Health, University Health Network; zHead, Multi-Organ Transplantation Psychosocial program, University Health Network; JUniversity of Toronto, Toronto, ON, Canada; yKing Saud University, Saudi Arabia; and zInstitute of Behavioral Sciences and 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary. Grant support: none. Dr Novak and Dr Alosaimi have no conflicts of interest. Dr Abbey is on the advisory board for Pfizer Canada, Eli Lilly Canada, and Lundbeck Canada and has also received research funding from Lundbeck Canada. Dr Sockalingam is a speaker for Roche Canada. Reprints: Sanjeev Sockalingam, MD, FRCPC, 200 Elizabeth Street— 8EN-225, Toronto General Hospital, University Health Network, Toronto, ON, Canada (e-mail: Sanjeev.Sockalingam@uhn.on.ca). CLINICAL REVIEW 38 | www.jcge.com J Clin Gastroenterol  Volume 44, Number 1, January 2010