The Trend of Psychiatric Side Effects in US Veterans with Hepatitis C and History of Psychiatric Disorder Receiving Interferon Based Therapy

Edward C. Paredez, David A. Blair, Vicki Sontag, Cynthia Geppert, Elizabeth Dettmer, Clifford Qualls, Antoine Jakiche



The majority of US veterans with hepatitis C (HCV) have a history of psychiatric disorder. Concern for worsening of psychiatric symptoms limits the eligibility for treatment in many of these patients.



The aim of this study is to identify trends of psychiatric side effects in patients with a history of significant psychiatric disorder (psych Hx) in comparison to patients without such history (control).



All patients with HCV treated at the Albuquerque VAMC multidisciplinary Hepatitis Clinic who reached a treatment endpoint between January 2002 through September 2003 were analyzed (n=40). A standardized template was used at each visit for collection of clinical and psychiatric data in addition to the CES-D (Center for Epidemiologic Studies-Depression) score at: baseline, week 2,4,8,12 and every 6 weeks thereafter. The outcomes analyzed were CES-D scores at each visit, addition or increase of psychiatric medications (Δ psych meds), completion of planned HCV therapy, and sustained viral response (SVR). Univariate analysis was performed using Fisher's Exact, Wilxcoxon and T-Tests. Multivariate analysis was performed using Poisson regression. All data was analyzed using SAS v8.02.



The mean CES-D scores were significantly higher in patients with psych Hx (n=26) compared to control patients (n=14) at baseline and at weeks 2, 4, 8 and 24 of treatment, but no difference in weeks 12, 18, and 30-48 (table). During treatment, patients with psych Hx had no significant change in CES-D score from baseline. In contrast, control patients had on average a 5.9% increase in CES-D score per visit. There were no differences between the two groups in rates of: Δ psych meds (73% vs 57%), treatment completion (62% vs 79%), and SVR (35% vs 50%) respectively.



1)     More than half of HCV veterans with or without psych Hx required an addition or increase of their psychiatric medications while receiving interferon based therapy.

2)     Patients with psych Hx did not have worsening of their depression based on the CES-D score, which may be due to the timely psychiatric interventions and adjustment of their psychiatric medications during treatment.

3)     Patients with psychiatric history did not have a decrease in the viral response or the rate of completion of HCV therapy.


Antidepressant Use in Veterans with Hepatitis C

Julie Nelligan, David W. Indest, Aaron D. Blackwell, Anna W. Sasaki, Marian Fireman, Peter Hauser



Approximately 6 to 7 % of veterans are infected with hepatitis C virus (HCV), and depression is a common co-morbid diagnosis. If left untreated, depression can be a cause of interferon treatment non-compliance or failure. This study examines antidepressant treatment rates in veterans with HCV prior to interferon treatment.



478 veterans (458 male, 20 female, 53.8 6.4 yrs) gave informed consent to monitor their treatment, and 379 (363 male, 16 female) completed a Beck Depression Inventory-II (BDI-II) as part of their initial HCV specialty clinic appointment. Review of pharmacy records yielded information regarding active prescriptions for psychotropic medications.



Of the 478 veterans enrolled in the study, 31.6% (151) were taking a psychotropic medication (prescribed for depression, anxiety, sleep difficulty, pain, psychotic symptoms, etc.). 27.6% (132) were taking an antidepressant, most frequently, an SSRI. Analgesics were the next most commonly prescribed drug, with 20.1% (96) taking an opioid and 6.7% (32) taking other analgesics.

Approximately one-third (129/379 or 34%) of veterans who completed the BDI-II scored 20 or higher, indicating a moderate to severe level of depression. Of note, of the 129 moderately or severely depressed patients, 72 (56%) were not taking an antidepressant and 44% (57) continued to experience moderate to severe depression despite taking anti-depressants. The 260 veterans not prescribed antidepressants upon enrollment had a significantly lower mean BDI-II score compared with the 119 veterans taking an antidepressant (14.2 vs. 19.1, p<.0001).


  • Depression is common among veterans with HCV, and in this sample, one-third had moderate to severe depression. Although antidepressants were the most commonly prescribed psychotropic medication, over half (56%) of moderately to severely depressed patients were not currently prescribed an antidepressant. Of the patients who had moderate to sever depression, 44% were on antidepressants suggesting that they were under-treated.
  • Because depression is a common reason for IFN dose modification or discontinuation screening and treatment is important in patients who are being considered for interferon therapy. Recent studies have shown that higher ratings of depression prior to initiating IFN treatment is related to increased symptomology during treatment.
  • Our study suggests that routine screening for psychiatric illness in HCV patients is warranted and will facilitate identification and treatment of depression.


Experience with Pegylated Interferon and Ribavirin Therapy in Patients with Hepatitis C in an Urban VA Hospital

Abhinandana Anantharaju, Linda Piersall, JoAnn Stegmaier, Bernard Nemchausky, Frank Iber, Nikunj Shah



Hepatitis C virus infection (HCV) is 10 times more prevalent in US veterans than in the general population. The interferon alfa 2b & ribavirin (R) therapy in veterans with HCV has a reported sustained viral response rate (SVR) of only 10%. The treatment with pegylated interferon (PI) & R is the current standard of therapy for HCV. The SVR using PI & R in veterans is unknown. In the general population, large registration trials using PI & R have reported an overall SVR of 54-56%. The SVR in genotype 1 patients being 42-44% & in genotype 2/3 78-80%.



We studied the efficacy of combination therapy with PI & R in veterans with HCV.



246 male HCV patients who began PIs (alfa 2a & 2b) and R combination therapy between May 2001 & April 2004 were evaluated. The PIs were used at standard recommended doses & Ribavirin was given at a dose of 11 mg/kg. Patients were followed closely in a dedicated multidisciplinary HCV clinic. Routine labs & HCV-RNA levels were monitored. Genotypes and pretreatment liver biopsies were obtained. Erythropoietin & filgrastim were used as necessary.



168 HCV patients completed the PI & R combination therapy. The mean age was 54.1 7.7 years. The Caucasians were 62.5%, African Americans 30.4%, & Hispanics 7.1%. 142 patients received PI-2b & 26 patients received PI-2a. The mean duration of therapy was 39.0 15.0 (range 2-48) weeks. Mean ALT & HCV RNA levels at entry were 104.6 76.3 U/L & 11.6 12.5 x 105 IU/ml resp. Patients with genotype 1, 2, & 3 were 80.4%, 11.3%, & 8.3% respectively. Fifty five (32.7%) patients had cirrhosis. Ninety four (55.9%) patients demonstrated early viral response (EVR). Of which, 73 (43.5%) patients experienced an end of therapy viral response (ETR). One hundred and forty one patients completed 24-week post-treatment follow-up. Overall SVR was noted in 44 (31.2%) patients. Among those who completed 48-week therapy (n = 91), the SVR was 43.9%. Two patients with SVR did not have EVR. The SVR in genotype 1, 2, & 3 patients were 26.3%, 66.7%, & 33.3% respectively. One hundred and three (61.3%) patients had 141 incidences of side effects related to therapy. The side effects included anemia (30.5%), psychiatric disturbances (19.1%), thrombocytopenia (5.1%), neutropenia (7.1%), & hypothyroidism (8.5%). 34 (20.2%) patients did not complete therapy due to side effects.



The US veterans with HCV show a better response (SVR by intent to treat 31.2%) to combination therapy with pegylated interferon and ribavirin than to standard interferon and ribavirin, but inferior response than the large registration trials.


HCV and HIV Coinfection: Impediments for Therapy

Moises A. Garcia, Nalini M. Guda, Ahmad B. Shughoury, Iram Nadeem, Aboud Affi



Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share similar risk factors for transmission. HIV co-infection accelerates the clinical course of HCV-related liver disease. A third of the co-infected are at risk of dying due to chronic liver disease. There are no HCV therapies specifically approved for patients co-infected with HIV. Preliminary data suggest successful eradication of HCV infection with currently available therapy. However, such studies have included few minority groups.



To determine prevalence, treatment and impediments, if any, for treatment of hepatitis C in a community clinic specializing in the care of indigent HIV infected population.



Retrospective chart review of 140 patients with HIV infection followed at a specialty clinic for treatment of HIV infected patients at Milwaukee, WI for the last five years. Trained reviewers collected the data in a specially abstracted data collection sheets. Data were analyzed using 2-sample tests, Mann-Whitney and chi square.



71 patients (50.7%) were HCV/HIV co-infected, 43 (30.7%) were HIV positive and HCV negative and 26 patients (18.5%) who were HIV positive were not evaluated for HCV. Among HCV/HIV co-infected patients 59.1% were males. The mean age was 45 years (Range 29-67). 47 patients (66.2%) were African American and 19 (26.7%) were Hispanics. HCV genotype 1 was found in 91% patients (68% genotype 1a, 23% genotype 1b). Overall, 6 HCV/HIV patients (8.4%) had liver biopsy, and 8 patients (11.2% - 3% IFN +RBV, 8% PEG IFN + RBV) were treated. Serum transaminases were significantly elevated despite similar usage of HAART therapy and alcohol use (see table). The most common reasons for co-infected patients not receiving hepatitis C virus therapy were: active continued use of alcohol (25.3%), significant psychiatric illness: (23.9%), discontinuation of care (25.3%), continued substance abuse (18.3%) and decompensated liver disease: 3 (4.2%). Depression was significantly higher in patients with co infection.



1. Co-infection with HIV/HCV is high in the community. 2. A significant number of patients with HIV were not tested for HCV co infection. 3. Only a small minority of the co-infected is treated even in specialized centers 4.Continued substance abuse, non-compliance and serious psychiatric problems are the major impediments for more aggressive treatment.





p value 

Duration HIV(years) 




CD4 count (L) 




ALT (U/L) 




AST (U/L) 




Albumin (GM/DL) 



Drugs Use: N(%) 

58 (81.6) 

9 (20.9) 


Alcohol Use: N(%) 




HAART: N(%) 




Depression: N(%) 





Histopathological Effects of Pegylated and Standard Interferon in Responders and Non Responders Chronic Hepatitis C Genotype 4

Gamal Esmat, Khalid Zalata, Mohamed Metwally, Mohamed Abdel Hamid, Amr Abouzied, Maissa El Raziky, Mohamed El Batanony, Thomas Strickland, Maria Sjogren



Egypt has a high prevalence of hepatitis C (HCV) (more than 10%) with predominant genotype 4 (more than 90%). Data about response to and histological benefit of interferon therapy in genotype 4 are limited. Aim: Study the histological effect of treatment with pegylated and standard interferon in chronic HCV genotype 4.



In a randomized controlled trial to study the effect of pegylated interferon alfa 2b/ribavirin against standard interferon/ribavirin, 100 patients were recruited to each arm. All patients had pretreatment liver biopsy and 97 (49 in pegylated group and 48 in standard group) had liver biopsy at week 72 of therapy. Demographic, laboratory and hisopathological data of liver biopsy (based on modified Ishac score) were collected. Regression of fibrosis or inflammation was defined as at least one stage decrease from the pretreatment stage or score.



Out of 97 patients, 56 (57.7%) had sustained virological response (SVR)(63.3% of pegylated group and 52.1% of standard group). Regression of fibrosis (decrease of fibrosis by at least one stage) was found in 39/97 (40.2%). Regression in fibrosis was not related to lower pre-treatment viral load, type of therapy or SVR (P=0.5, 0.3 and 0.2 respectively). Regression of inflammatory activity was found in 74/97 (76.3%). Regression of inflammatory activity was significantly associated with SVR (P=0.0001). In summary, in logistic regression analysis, the only independent predictor for regression of inflammatory activity is the presence of SVR (p=0.001)



1) A substantial number of patients had regression of fibrosis and inflammation either treated with standard or pegylated IFN.

2) Patients with SVR had more regression in inflammation than patients with no SVR; however both groups had equal regression of fibrosis.

3) Long term benefit from the regression in responders and non responders should be studied.