Comorbid medical and psychiatric conditions and substance abuse in HCV infected persons on dialysis *

Transcription

1 Journal of Hepatology 44 (2006) Comorbid medical and psychiatric conditions and substance abuse in persons on dialysis * Adeel A. Butt 1,2,3, *,, Robert Evans 1, Melissa Skanderson 2, A. Obaid Shakil 1 1 University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 2 VA Pittsburgh Healthcare System, Pittsburgh, PA, USA 3 Center for Health Equity Research and Promotion, Pittsburgh, PA, USA See Editorial, pages Background/Aims: The burden of comorbidity in the Hepatitis C virus (HCV) infected persons on dialysis is unknown. Methods: We identified all and uninfected subjects in the United States Renal Data System in the years using ICD-9 codes. Controls were matched on the date of first dialysis. ICD-9 codes and claims data was used to identify medical and psychiatric comorbidities. Results: We identified 5,737 persons and 11,228 subjects. subjects were younger, more likely to be black race and male and more likely to have the following comorbidities: hypertension; hepatitis B; cirrhosis; wasting; anemia; human immunodeficiency virus (HIV) infection; major depression; mild depression; bipolar disorder; schizophrenia; post-traumatic stress disorder; drug use; alcohol use; smoking and less likely to have the following comorbidities: coronary artery ; stroke; peripheral vascular ; diabetes; cancer; erythropoietin use. After adjusting for age, gender and race, subjects were more likely to have hypertension, hepatitis B, cirrhosis, wasting, anemia and HIV infection and less likely to have coronary artery and stroke. Conclusions: persons on dialysis are more likely to have psychiatric comorbidities and substance abuse, as well as certain medical comorbidities. These factors should be considered when developing future intervention strategies. q 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Keywords: HCV; Dialysis; Comorbidities; Treatment 1. Introduction Received 27 September 2005; received in revised form 6 January 2006; accepted 17 January 2006; available online 20 February 2006 * The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government. * Corresponding author. Address: Falk Medical Building, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Suite 3A, Pittsburgh, PA 15213, USA. Fax: C address: butta@dom.pitt.edu (A.A. Butt). Funding: Dr Butt is the recipient of a Career Development Award from the National Institutes of Health/National Institute on Drug Abuse (DA A1). Dr Butt had had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Hepatitis C virus (HCV) infection is a major cause of morbidity and is the leading reason for liver transplants in the United States [1,2]. The prevalence of HCV is higher in certain populations, including persons infected with the human immunodeficiency virus (HIV), veterans in care at the Veterans Affairs (VA) medical centers in the United States and persons on hemodialysis [3 6]. Treatment choices for HCV are limited and successful eradication of infection is achieved only in 54 56% of the treated persons in clinical trials [7 13]. Renal failure is a contraindication to HCV treatment since ribavirin is associated with a dose dependent hemolytic anemia which is prolonged and may be /$32.00 q 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi: /j.jhep

2 A.A. Butt et al. / Journal of Hepatology 44 (2006) life threatening in patients with renal failure. In addition, presence of medical and psychiatric comorbid conditions are among the leading reasons for non-treatment of HCV in the infected persons [14,15]. The burden of comorbid medical and psychiatric conditions in patients with renal failure who are on dialysis has not been described. Presence of multiple comorbidities may potentially provide additional reasons for withholding treatment in this population. We used a national population of patients on dialysis to determine the rates of comorbidities in and uninfected persons. 2. Methods We assembled a cohort of HCV-infected subjects and HCV-uninfected controls from 1997 to 1998 United States Renal Data System (USRDS) population. The details of the USRDS have been described elsewhere [16] and are also available on the USRDS web site ( The overall demographics of the USRDS population, incident and prevalent cases, medical comorbidities and mortality rates have been described in the 2004 Annual Data report of the USRDS. Briefly, the objective of the USRDS is to gather and create an integrated database system for outcomes research. The data in the USRDS is gathered from several sources, which include Center for Medicare and Medicaid Services, United Network for Organ Sharing, Centers for Disease Control and Prevention and the End Stage Renal Disease Networks, as well as special studies conducted by the USRDS. More than 1.5 million persons have been treated through this program since its inception over 20 years ago [16]. We identified subjects through the USRDS claims files using ICD-9 codes. The use of ICD-9 codes for identifying persons has been validated in other large administrative cohorts by our group and others [17 21]. In Veterans Aging Cohort Study, the agreement between laboratory diagnosis of HCV and the ICD-9 codes was 78% (kappa 0.42) and the positive predictive value was 94% [17]. Kramer et al. also reported the positive predictive value of the ICD-9 diagnosis to be 94% and the negative predictive value of 90% [19]. HCV infection was defined as having at least two outpatient or one inpatient ICD-9 diagnostic code for HCV or related diagnoses in For each person, we identified up to two controls matched on the month of the first claim for HCV. Medical and psychiatric comorbidities and substance abuse were determined from the USRDS files (where they are listed as diagnoses) as well as ICD-9 codes in the claims files followed through September We limited our study population to persons on hemodialysis and excluded subjects with a renal transplant at any time or if they were!18 years old or O90 years old. Analyses were conducted using Stata 8.2. (Stata Corporation, College Station, TX) The t-test was used to compare age and chi-square tests were used to compare race, gender and presence of comorbidities between HCVinfected and uninfected groups. Logistic regression was used to determine the adjusted and unadjusted odds of comorbid conditions attributable to HCV infection. 3. Results We identified 5,737 persons and 11,228 persons using the criteria listed above. The mean age was 57.8 years for the and 65.3 years for the subjects (P!0.0001), 57.6% of the and 42.4% of the HCV uninfected subjects were male. Among the subjects, 39.3% were White, 54.0% were Black, while among the subjects, 57.9% were White and 36.4% were Black (P!0.0001) (Table 1). Table 1 Demographics of and uninfected persons on dialysis (nz5,737) (nz11,228) P-value Age Mean (years) ! Race (%) White ! Black Other/ Unknown Gender (% male) ! Body mass index Mean time on dialysis before HCV diagnosis (mean (median) years) 3.02 (1.86) 2.82 (1.88) The 15 most common primary s that led to renal failure are listed in Table 2. There were significant differences in the overall prevalence of major medical and psychiatric comorbidities, as well as drug and alcohol use (Table 3). The following were more prevalent in the HCV infected persons: hypertension; hepatitis B; cirrhosis; wasting; anemia; HIV infection; major depression; mild depression; bipolar disorder (PZ0.01) schizophrenia; posttraumatic stress disorder; drug use; alcohol use; and smoking (PZ0.01) [P! for all except where indicated]. The following conditions were less prevalent in the subjects: coronary artery ; stroke; peripheral vascular ; diabetes; cancer (PZ 0.01); and erythropoietin use [P! for all except where indicated]. Table 2 Most common causes of renal failure in the and uninfected persons on dialysis Adult onset, Type diabetes Hypertension Glomerulonephritis Juvenile onset, Type diabetes Focal glomerulosclerosis AIDS nephropathy Adult polycystic Chronic interstitial nephritis Acquired obstructive nephropathy Lupus nephropathy Tubular necrosis Renal artery stenosis Cholesterol emboli Missing

3 866 A.A. Butt et al. / Journal of Hepatology 44 (2006) Table 3 Prevalence of co-morbidities in and uninfected persons on dialysis We calculated unadjusted and adjusted odds ratios for these comorbidities. Adjustment was made for age, gender and race (Table 4). The following comorbidities had a higher odds of being present in the persons after adjustment for age, gender and race: hypertension; hepatitis B; cirrhosis; wasting; anemia; and HIV infection. The following comorbidities had a lower odds of being present in the subjects after adjusting for age, gender and race: coronary artery ; and stroke. The following conditions were associated with a lower odds of being present in the subjects in the unadjusted model, but were not statistically significant after adjusting for age, gender and race: stroke and diabetes (for odds ratios and 95% confidence intervals (CI); see Table 4). Subjects with HCV infection were more likely to have O 6 comorbid conditions compared with subjects, and were less likely to have no comorbid conditions (overall P!0.0001) (Fig. 1). 4. Discussion (nz5,737) (nz11,228) P-value Medical comorbidities Coronary artery ! Hypertension ! Stroke ! Peripheral vascular ! Diabetes ! Hepatitis B ! Cirrhosis ! Wasting ! Cancer Anemia ! Erythropoietin use ! HIV ! Psychiatric comorbidities Major Depression ! Mild depression ! Bipolar disorder Schizophrenia ! Post-traumatic stress disorder Substance abuse Drug use ! Alcohol use ! Smoking ! Values are percentages. We demonstrated that persons with end stage renal who are on dialysis had significant differences in their demographic characteristics and the prevalence of comorbidities compared with HCV Table 4 Unadjusted and adjusted odds ratios of comorbid conditions in HCVinfected persons on dialysis Unadjusted odds ratios (95% CI) Adjusted odds ratios a (95% CI) Medical comorbidities Coronary artery 0.64 ( ) 0.83 ( ) Hypertension 1.44 ( ) 1.44 ( ) Stroke 0.83 ( ) 1.01 ( ) Peripheral vascular 0.72 ( ) 0.88 ( ) Diabetes 0.91 ( ) 0.99 ( ) Hepatitis B ( ) 9.08 ( ) Cirrhosis ( ) 9.63 ( ) Wasting 1.45 ( ) 1.48 ( ) Cancer 0.76 ( ) 1.14 ( ) Anemia 1.92 ( ) 2.01 ( ) Erythropoietin use 0.75 ( ) 0.91 ( ) HIV 4.39 ( ) 2.58 ( ) Psychiatric comorbidities Major Depression 1.32 ( ) 1.17 ( ) Mild depression 1.21 ( ) 1.18 ( ) Bipolar disorder 1.44 ( ) 1.19 ( ) Schizophrenia 1.84 ( ) 1.42 ( ) Post-traumatic 3.68 ( ) 2.45 ( ) stress disorder Substance abuse Drug use 4.06 ( ) 2.80 ( ) Alcohol use 5.05 ( ) 3.59 ( ) Smoking 1.92 ( ) 1.59 ( ) a Adjusted for age, gender and race. uninfected persons. The persons were younger, more likely to be Black race and male. This is in line with demographic characteristics of persons in other populations. We found that the persons had a lower prevalence of certain medical comorbidities that are generally associated with vascular and atherosclerotic. These included coronary artery, stroke and peripheral vascular. The reason for this is unclear. Increasing age, male gender and minority race are risk factor for these conditions, but the lower association of % with comorbidities >6 Number of comorbidities Fig. 1. Number of co-morbidities by HCV infection status. [This figure appears in colour on the web.]

4 A.A. Butt et al. / Journal of Hepatology 44 (2006) coronary artery and peripheral vascular with HCV remained significant even after adjusting for these characteristics. Whether there are other etiologic factors or risk factors in persons with end stage renal is not known. Diabetes, hypertension and smoking are other risk factors for coronary artery. However, the lower risk of these conditions persisted even after adjusting for hypertension, diabetes and smoking, in addition to age, gender and race (results not shown). The overall prevalence of hepatitis B, HIV and cirrhosis was higher in the subjects. This is expected due to the shared routes of transmission for these viral infections, and the well-known effects of HCV and hepatitis B upon development of advanced liver. Anemia was more likely to be present in persons, and this effect persisted after adjusting for age, gender and race. There have been case reports of autoimmune anemia in patients with HCV, but whether that is responsible for the increased prevalence in our study is not known [22 25]. Psychiatric illness and substance abuse were more common in persons. Again, this is consistent with studies in other populations with HCV infection. Whether drug use and alcohol use preceded HCV infection or was current and ongoing is not known. These associations persisted after adjusting for age, gender and race. The standard of care for treatment of HCV is a combination of interferon alfa and ribavirin. Ribavirin is associated with a dose dependent hemolytic anemia and is contraindicated in patients with end stage renal. However, there is some data that treatment with interferon alone may lead to eradication of HCV in a significant number of patients with end stage renal [26]. Additionally, treatment is contraindicated in persons with active depression, severe anemia and active drug and alcohol use. The high prevalence of these conditions in persons with end stage renal should be taken into account when developing future guidelines or clinical trials for treatment of HCV in this population. The strengths of our study include large numbers of a nationally representative population, rather than a geographically limited or a convenience sample and presence of a group to compare the comorbidities. To our knowledge, this is the first and largest study of this kind in patients with end stage renal, and would have implications when developing clinical guidelines for management of persons with end stage renal. There are certain limitations to our study. We identified persons based on ICD-9 codes. While this may have led to a lower number of persons with HCV being identified, it may also have biased the sample towards more sicker patients, or those with more advanced liver. This is a retrospective analysis, where comorbidities were also identified using ICD-9 codes and claims data. In conclusion, persons on dialysis are more likely to have psychiatric comorbidities and substance abuse, as well as certain medical comorbidities including hypertension, hepatitis B, anemia and HIV. These factors should be considered when developing future intervention strategies and guidelines for treatment of HCV in this population. Future prospective studies should address how these comorbidities affect outcomes and whether psychiatric illness and drug and alcohol use are active problems in this population. References [1] Tong MJ, El Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995;332: [2] Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 2000;132: [3] Center for Disease Control and Prevention. 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