2
compare changes in these problems over time in patients both on and off antiviral therapy. Methods: Twenty-four patients with chronic HCV, 12 about to undergo anti-viral therapy and 12 not undergoing antiviral therapy, were matched as closely as possible on age, gender, ethnicity, fibrosis stage, and current management with psychotropic medication. All patients completed the Beck Depression Inventory-II, Beck Anxiety Inventory, and Multidimen- sional Assessment of Fatigue scale at baseline and at approximately 3 and 6 months post-baseline. A repeated measures multivariate analysis of variance (MANOVA) was used to determine significant between and within group differences. Results: Average scores and standard deviations for all measures across time are presented by group in the table. There was no significant main effect of group or time. The group by time interactions for depression and anxiety were not significant, while the group by time interaction for fatigue nearly reached statistical significance (p .056). No Treatment Group Antiviral Therapy Group Baseline 3 months 6 months Baseline 3 months 6 months Depression 16.3 (9.4) 14.7 (10.9) 15.6 (15.1) 14.5 (8.6) 12.2 (9.0) 14.9 (7.9) Anxiety 13.7 (9.5) 12.7 (11.4) 11.9 (10.9) 9.3 (9.3) 8.2 (8.1) 11.0 (8.6) Fatigue 26.5 (14.8) 26.6 (16.0) 30.6 (16.2) 23.5 (15.4) 25.4 (13.0) 29.0 (11.7) Note: Higher scores indicate greater severity on all measures. Conclusions: 1) Depression and anxiety do not change significantly over the first 6 months of antiviral therapy. In contrast, fatigue increases sig- nificantly during the first 6 months of treatment. 2) Identification of effec- tive treatment strategies for fatigue is critical, as is proper management of depression and anxiety prior to initiation of antiviral therapy. 382 Octreotide and albumin infusion in the treatment of decompensated end stage liver disease and oliguria Tarek I Hassanein, MD 1 *, Omaran Abdeen, MD 2 , Rhonda Martin, NP 2 , Ajai Khanna, MD 3 , Marquis Hart, MD 3 and Ravindra Mehta, MD 2 . 1 Departments of Medicine and Surgery; 2 Department of Medicine; and 3 Department of Surgery, University of California, San Diego, San Diego, CA, United States. Purpose: Acute renal failure with oliguria is a terminal presentation in patients with decompensated end stage liver disease (ESLD). The spectrum of renal insufficiency extends from pre-renal azotemia to hepatorenal syndrome. Survival is significantly compromised in patients who develop renal failure in the course of ESLD. Methods: We studied 14 consecutive patients with oliguric renal failure complicating decompensated ESLD. Patients had a mean urine output of 537 cc/d, mean serum creatinine of 3.4 mg/dL and BUN of 73 mg/dL. All patients received intravenous Octreotide drips at a mean rate of 39 mcg/h for a mean period of 7.4 days. In addition, all patients had serum albumin concentration 3 gm/L by infusion of albumin 25% as needed. Midodrine was added to the regimen at a mean daily dose of 23 mcg/d. Results: Total serum albumin concentration at the beginning of the Oct- reotide infusion was 2.8 gm/L. Urine output improved to 1921 cc/d within 48 hours (p 0.005). Serum creatinine and BUN levels showed no significant changes within the first five days of treatment. All patients tolerated treatment well. Sixty-four percent (9/14) of patients required renal support. Hospital mortality was 50%. The one-month mortality was only 57%. Conclusions: 1) The combination of intravenous Octreotide and albumin and oral Midodrine is highly effective in treating acute renal failure in decompensated ESLD patients. 2) This combination therapy had a positive impact on hospital survival of decompensated patients. 383 Relationship of chronic HCV infection, intravenous drug use, and psychiatric history to depression and anxiety Robin C Hilsabeck, Ph.D. 1 , Meghan D Carlson 1 , Beth A Ziegler, M.S. 1 , Nina Aronson, B.S. 1 , Eileen Chatfield, M.A. 1 , William Perry, Ph.D. 2 and Tarek I Hassanein, M.D. 1 *. 1 Department of Medicine, University of California, San Diego, San Diego, CA, United States; and 2 Department of Psychiatry, University of California, San Diego, San Diego, CA, United States. Purpose: Depression and anxiety are highly prevalent in individuals in- fected with the hepatitis C virus (HCV). The purpose of this study was to examine the relationships of chronic HCV, history of intravenous drug use (IVDU), and psychiatric history to current mood status. Methods: Sixty-five patients with chronic HCV (62% with a history of IVDU), 22 patients with other types of chronic liver disease (50% with a history of IVDU), and 15 individuals without chronic liver disease (100% with a history of IVDU) participated in this study. There were no group differences in age, gender, or ethnicity. Fibrosis stage did not differ sig- nificantly between the chronic liver disease groups. None of the HCV- infected participants were on anti-viral therapy. All participants completed the Beck Depression Inventory-II and Beck Anxiety Inventory. Results: There were no significant group differences in depression or anxiety. Thus, the groups were collapsed for the remaining analyses. No significant differences in depression or anxiety were found between par- ticipants with and without a history of IVDU; however, there was a significant difference in depression and anxiety between patients with and without a history of psychiatric problems. Further, patients with histories of both psychiatric problems and IVDU reported the greatest levels of mood impairment, and patients with no history of either reported the least (see table). Table. Average Scores (Standard Deviations) for Depression and Anxiety by Group Depression Anxiety No Past Psych/IVDU 12.8 (7.5) 9.6 (8.0) No Past Psych/IVDU 13.3 (11.8) 10.7 (10.6) Past Psych/IVDU 17.3 (10.5) 12.6 (9.1) Past Psych/IVDU 20.8 (10.5) 17.2 (9.8) Depression–normal (0 –13), mild (14 –19), moderate (20 –25), severe (26) Anxiety– normal (0 –7), mild (8 –15), moderate (16 –23, severe (24) Conclusions: 1) Patients with chronic liver disease experience mild levels of depressive and anxious symptoms regardless of etiology. Thus, depres- sion and anxiety should be evaluated and monitored in all patients with chronic liver disease. 2) Depression and anxiety do not differ in patients with and without histories of IVDU. 3) Depression and anxiety are greater in patients with past psychiatric problems, and patients with a history of both psychiatric problems and IVDU report the most significant mood disturbance. 384 The role of glucocorticoid receptors in interferon induced depression Raouf E Hilal, Charley Chung, V Khaoustov and Boris Yoffe*. 1 Gastroenterology, VA Medical Center and Baylor College of Medicine, Houston, Texas, United States. Purpose: Significant neuropsychiatric side effects of interferon (IFN)- based therapy are prevalent and carry a substantial risk for suicide, lead to medication non-compliance and may require dose reduction or cessation of treatment. Major depressive disorder (MDD) has been linked to a dysfunc- tional hypothalamic-pituitary-adrenal (HPA) axis as reflected by the glu- cocorticoid receptors (GCR). Low levels of lymphocyte GCR correlate with depressive symptoms. Aims: 1) To document the frequency and impact of psychiatric side effects in patients enrolled in an IFN-based therapy for HCV. 2) To assess the S122 Abstracts AJG – Vol. 96, No. 9, Suppl., 2001

The role of glucocorticoid receptors in interferon induced depression

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compare changes in these problems over time in patients both on and offantiviral therapy.Methods: Twenty-four patients with chronic HCV, 12 about to undergoanti-viral therapy and 12 not undergoing antiviral therapy, were matched asclosely as possible on age, gender, ethnicity, fibrosis stage, and currentmanagement with psychotropic medication. All patients completed theBeck Depression Inventory-II, Beck Anxiety Inventory, and Multidimen-sional Assessment of Fatigue scale at baseline and at approximately 3 and6 months post-baseline. A repeated measures multivariate analysis ofvariance (MANOVA) was used to determine significant between andwithin group differences.Results: Average scores and standard deviations for all measures acrosstime are presented by group in the table. There was no significant maineffect of group or time. The group by time interactions for depression andanxiety were not significant, while the group by time interaction for fatiguenearly reached statistical significance (p � .056).

No Treatment Group Antiviral Therapy Group

Baseline 3 months 6 months Baseline 3 months 6 months

Depression 16.3 (9.4) 14.7 (10.9) 15.6 (15.1) 14.5 (8.6) 12.2 (9.0) 14.9 (7.9)Anxiety 13.7 (9.5) 12.7 (11.4) 11.9 (10.9) 9.3 (9.3) 8.2 (8.1) 11.0 (8.6)Fatigue 26.5 (14.8) 26.6 (16.0) 30.6 (16.2) 23.5 (15.4) 25.4 (13.0) 29.0 (11.7)

Note: Higher scores indicate greater severity on all measures.

Conclusions: 1) Depression and anxiety do not change significantly overthe first 6 months of antiviral therapy. In contrast, fatigue increases sig-nificantly during the first 6 months of treatment. 2) Identification of effec-tive treatment strategies for fatigue is critical, as is proper management ofdepression and anxiety prior to initiation of antiviral therapy.

382

Octreotide and albumin infusion in the treatment of decompensatedend stage liver disease and oliguriaTarek I Hassanein, MD1*, Omaran Abdeen, MD2, Rhonda Martin, NP2,Ajai Khanna, MD3, Marquis Hart, MD3 and Ravindra Mehta, MD2.1Departments of Medicine and Surgery; 2Department of Medicine; and3Department of Surgery, University of California, San Diego, SanDiego, CA, United States.

Purpose: Acute renal failure with oliguria is a terminal presentation inpatients with decompensated end stage liver disease (ESLD). The spectrumof renal insufficiency extends from pre-renal azotemia to hepatorenalsyndrome. Survival is significantly compromised in patients who developrenal failure in the course of ESLD.Methods: We studied 14 consecutive patients with oliguric renal failurecomplicating decompensated ESLD. Patients had a mean urine output of537 cc/d, mean serum creatinine of 3.4 mg/dL and BUN of 73 mg/dL. Allpatients received intravenous Octreotide drips at a mean rate of 39 mcg/hfor a mean period of 7.4 days. In addition, all patients had serum albuminconcentration � 3 gm/L by infusion of albumin 25% as needed. Midodrinewas added to the regimen at a mean daily dose of 23 mcg/d.Results: Total serum albumin concentration at the beginning of the Oct-reotide infusion was 2.8 gm/L. Urine output improved to 1921 cc/d within48 hours (p � 0.005). Serum creatinine and BUN levels showed nosignificant changes within the first five days of treatment. All patientstolerated treatment well. Sixty-four percent (9/14) of patients required renalsupport. Hospital mortality was 50%. The one-month mortality was only57%.Conclusions: 1) The combination of intravenous Octreotide and albuminand oral Midodrine is highly effective in treating acute renal failure indecompensated ESLD patients. 2) This combination therapy had a positiveimpact on hospital survival of decompensated patients.

383

Relationship of chronic HCV infection, intravenous drug use, andpsychiatric history to depression and anxietyRobin C Hilsabeck, Ph.D.1, Meghan D Carlson1, Beth A Ziegler, M.S.1,Nina Aronson, B.S.1, Eileen Chatfield, M.A.1, William Perry, Ph.D.2 andTarek I Hassanein, M.D.1*. 1Department of Medicine, University ofCalifornia, San Diego, San Diego, CA, United States; and 2Departmentof Psychiatry, University of California, San Diego, San Diego, CA,United States.

Purpose: Depression and anxiety are highly prevalent in individuals in-fected with the hepatitis C virus (HCV). The purpose of this study was toexamine the relationships of chronic HCV, history of intravenous drug use(IVDU), and psychiatric history to current mood status.Methods: Sixty-five patients with chronic HCV (62% with a history ofIVDU), 22 patients with other types of chronic liver disease (50% with ahistory of IVDU), and 15 individuals without chronic liver disease (100%with a history of IVDU) participated in this study. There were no groupdifferences in age, gender, or ethnicity. Fibrosis stage did not differ sig-nificantly between the chronic liver disease groups. None of the HCV-infected participants were on anti-viral therapy. All participants completedthe Beck Depression Inventory-II and Beck Anxiety Inventory.Results: There were no significant group differences in depression oranxiety. Thus, the groups were collapsed for the remaining analyses. Nosignificant differences in depression or anxiety were found between par-ticipants with and without a history of IVDU; however, there was asignificant difference in depression and anxiety between patients with andwithout a history of psychiatric problems. Further, patients with histories ofboth psychiatric problems and IVDU reported the greatest levels of moodimpairment, and patients with no history of either reported the least (seetable).

Table. Average Scores (Standard Deviations) for Depression and Anxiety by Group

Depression Anxiety

No Past Psych/IVDU� 12.8 (7.5) 9.6 (8.0)No Past Psych/IVDU� 13.3 (11.8) 10.7 (10.6)Past Psych/IVDU� 17.3 (10.5) 12.6 (9.1)Past Psych/IVDU� 20.8 (10.5) 17.2 (9.8)

Depression–normal (0–13), mild (14–19), moderate (20–25), severe (26�) Anxiety–normal (0–7), mild (8–15), moderate (16–23, severe (24�)

Conclusions: 1) Patients with chronic liver disease experience mild levelsof depressive and anxious symptoms regardless of etiology. Thus, depres-sion and anxiety should be evaluated and monitored in all patients withchronic liver disease. 2) Depression and anxiety do not differ in patientswith and without histories of IVDU. 3) Depression and anxiety are greaterin patients with past psychiatric problems, and patients with a history ofboth psychiatric problems and IVDU report the most significant mooddisturbance.

384

The role of glucocorticoid receptors in interferon induced depressionRaouf E Hilal, Charley Chung, V Khaoustov and Boris Yoffe*.1Gastroenterology, VA Medical Center and Baylor College of Medicine,Houston, Texas, United States.

Purpose: Significant neuropsychiatric side effects of interferon (IFN)-based therapy are prevalent and carry a substantial risk for suicide, lead tomedication non-compliance and may require dose reduction or cessation oftreatment. Major depressive disorder (MDD) has been linked to a dysfunc-tional hypothalamic-pituitary-adrenal (HPA) axis as reflected by the glu-cocorticoid receptors (GCR). Low levels of lymphocyte GCR correlatewith depressive symptoms.Aims: 1) To document the frequency and impact of psychiatric side effectsin patients enrolled in an IFN-based therapy for HCV. 2) To assess the

S122 Abstracts AJG – Vol. 96, No. 9, Suppl., 2001

Page 2: The role of glucocorticoid receptors in interferon induced depression

presence of GCR on cultured hepatocytes and T-lymphocytes and thepossible modulation of GCR levels by IFN.Methods: Ten HCV(�) patients on FDA-approved IFN-based therapywere chosen because of they completed the Beck Depression Inventory(BDI) assessment and were monitored for clinical depression as well asmedical non-compliance and response to antidepressant therapy. In vitro,hepatoblastoma and T-lymphocyte cells are analyzed for GCR levels usingWestern blot analysis after incubation (6, 24, and 48 hours) with increasingIFN concentrations.Results: Of the ten HCV(�) patients, 20% showed sustained virologicresponse, 50–60% developed clinical depression, and medical non-com-pliance was observed in 20%. Severe depression requiring termination ofIFN therapy occurred in 10% and 56% required concomitant antidepressanttherapy. Generally, depression as reflected by increased BDI score, ap-peared between weeks 6–22 on IFN-based treatment. In vitro, both culturedhepatocytes and T-lymphocytes showed a dose-dependent decrease of GCRlevels after incubation with IFN at 24 hours (but not at 6 or 48 hours).Conclusions: 1) IFN-induced depression is prevalent in HCV treatedpatients and can lead to medical noncompliance or discontinuation oftreatment. 2) In vitro, we demonstrated that GCR is present in hepatoblas-toma cell line, and that IFN decreases both T-lymphocyte and hepatocyteGCR density after 24 hours of incubation (unreported in the currentliterature). 3) We are currently assessing GCR levels in HCV (�) patientsand disruption of the HPA axis via downregulation of the GCR density asa possible link to IFN-induced depression.

385

Usefulness of enhanced ultrasonography (coded harmonic angio) toevaluate therapeutic effects of hepatocellular carcinomaNaoki Hotta, Yoshitaka Fukuzawa, Kagumi Yoshida, Tsuneaki Tagaya,Akihiko Okumura, Tetsuya Ishikawa and Shinichi Kakumu*.1Gastroenterology, Aichi Medical University, Nagakute, Japan.

Purpose: Harmonic imaging with the use of cotrast-enhance Coded Har-monic Angio(CHA) is a new contrast imaging technique for various solidtumors. In this study, we compared the imaging effects of HCC by intra-venus ultrasound Galactose-based contrast agent (LevovistTM, ScheringAG, Berlin, Germany) with those by conventional method. In addtion, wecompared the efficacy of CHA with other harmonic imaging (contrast-enhanced harmonic Power Doppler, contrast-enhanced Color Doppler) toexplore more sensitive and convenient examination for evaluating theeffects of anti-tumor therapy.Methods: Twenty-one patients with hepatocellular carcinoma (HCC) wereincluded in this study. The diagnosis of HCC was done by angiography, CTangiography and/or tumor biopsy. LevovistTM was injected intavenouslyas a bolus using 20-gauge peripheral intravenous cannula with an injectionspeed of 1ml/sec, and images obtained by US machine LOGIQ 700EX-PERT Series (GE medical Systems, Milwaukee) were compared with thosewithout any contrast agents. We examined contrast-enhanced harmonicPower Doppler, contrast-enhanced Color Doppler and CHA on each HCC.HCCs positive for tumor vascularity and feeding artery at CHA weretreated with either percutaneous ethanol injection therapy (PEIT) or radio-frequency ablation (RFA). Evaluation of anti-tumor procedure was done byCHA using LevovistTM as well as contrast-enhanced CT.Results: Nineteen out of 22 tumors (86%) were positively stained by CHA(diffuse: 14, spotty: 5), whereas 12 (54.5%) and 11 (50%) tumors werepositively stained by Harmonic Power Doppler method and Contrast-enhanced Color Doppler method, respectively. Nine HCCs were treatedwith RFA and 13 HCCs with PEIT under the direction of CHA. Disap-pearance of residual blood flow was confirmed by CHA right after thetreatment. After successful treatment, CHA signals were no longer detect-able, but CHA signals were still recognized in lesions containing residualviable carcinomatous tissue. In the evaluation after anti-tumor therapy,CHA using LevovistTM was as sensitive as contrast-enhanced CT.

Conclusions: Contrast-enhanced CHA is an another effective US tech-nique in evaluating the vascularity of HCC. Thus, this techneique seems tobe quite useful to evaluate the effectiveness of anti-HCC treatment.

386

Minimal change glomerulopathy with interferon treatment in apatient with hepatitis CMeng Hua, MD; Kevin B. Mercure; James G. Kohlroser, DO andRichard P. MacDermott, MD. Division of Gastroenterology, AlbanyMedical College, Albany, New York.

We report the first case of minimal change nephrotic syndrome and acuterenal failure in a patient with chronic hepatitis C due to INF-alpha. A48-year-old African American male with known history of hepatitis B,hepatitis C, hypertension and hyperlipidemia presented to the hospital withabdominal pain, nausea, vomiting, diarrhea and abdominal distension of 3weeks duration. He gained approximately 11 lbs. in 2 weeks prior toadmission. One month prior to admission he had been treated with a 3 weekcourse of Interferon (INF-alpha) therapy for Hepatitis C. His past historywas significant for IVDA and tobacco abuse. On examination he was foundto have abdominal distension, right upper abdominal tenderness, hepato-splenomegaly and normoactive bowel sounds. The cardiac, lung, neuro-logic examination was normal. On admission, laboratory data showedWBC 7.8 k/ul, BUN 107 mg/dl, Creatinine 13.2 mg/dl, albumin �1.0 g/dl,AST 22 iu/l, ALT 15 iu/l. Further testing showed a 24-hour urine protein36 grams, no paraproteinemia on SPEP. The abdominal CAT scan showedascites. A paracentesis showed pH of 7.36, protein �1.0 g/dl, LDH 22 iu/l,WBC 0.006 k/ul (neutrophils 15). A renal biopsy was done which showedchanges consistent with minimal change disease associated with changes ofbenign nephrosclerosis. Direct immunofluorescence demonstrated no stain-ing for IGG, IgA, IgM, C1Q, C3 or C4. The temporal relationship oftreatment with INF-alpha made renal failure most likely secondary to INFtherapy. Patient was managed with 5 sessions of hemodialysis and highdose steroids with improvement of renal function. The development ofminimal change glomerulopathy in patients with cutaneous T-cell lym-phoma or mycosis fungoides after INF-alpha treatment has been reported.These patients were treated with 24–100 million units T.I.W. The patho-genesis of the renal failure is unclear. A nephrologic work up should beundertaken if proteinuria detected during therapy with interferon.

387

Tissue pyrimidine nucleoside phosphorylase levels in metastatic livertumor of large bowel cancerTatsumi Iida MD*, Masahiro Gotoh, Noritake Mizutani and ToshiyukiMiyahara. 1Surgery, Yoro Cental Hospital, Yoro-Gun, Gifu-Pref.,Japan.

Purpose: In the present study, we determined PyNPase levels in tissuespecimens obtained from patients with large bowel cancer and metastatichepatic tumor, and compared PyNPase levels between tumor tissues andnormal surrounding tissues to evaluate whether PyNPase determinationmay aid in predicting the therapeutic effects of treating progressive cancerwith 5�-DFUR in the future.Methods: Subjects consisted of 21 patients including 15 male and 6 femalepatients. PyNPase levels in the primary tumor foci and normal surroundingtissues were determined. PyNPase levels in tumorous and normal regionsof the liver were also determined. Each tissue specimen weighing approx-imately 0.5 g was examined by ELISA. Statistical analysis was performedby Student t-test.Results: The mean PyNPase level in tissue specimens obtained from theprimary tumor foci was 75.3plusminus41.0unit/mg protein, while that innormal surrounding tissues was40.5plusminus24.4unit/mg protein. Themean PyNPase level in the primary tumor foci was significantly higher thanthat in normal surrounding tissues (p � 0.006). The mean PyNPase levelin metastasized hepatic tumor tissues was 56.3 � 43.4 unit/mg protein,while that in normal surrounding tissues was 21.5 � 20.4 unit/mg protein.

S123AJG – September, Suppl., 2001 Abstracts