Immune alterations and profile of lymphocyte subsets in treatment resistant chronic hepatitis C...
1
273 AUTOIMMUNE CHOLANGITIS MANIFESTING AS CUTANEOUS LYMPHOCYTIC VASCULITIS OF THE LOWER EXTREMITIES Alex R. Rusynyk, D.O., Michael J. Komar, M.D.* and Matthew B. Grundfast, D.O. Gastroenterology and Nutrition, Geisinger Medical Center, Danville, PA. Background: Autoimmune cholangitis is a rare disorder in which patients exhibit histologic features suggesting primary biliary cirrhosis, but are often seronegative for antimitochondrial antibody (AMA), and tend to have circulating antinuclear antibodies (ANA). We report a case of autoimmune cholangitis diagnosed in a 43–year– old female with a recurrent lower extremity rash. Case Report: A 43–year– old white female presented to her PCP with a bilateral lower extremity erythematous rash and arthralgias. Her past med- ical history was unremarkable, and she was not taking any medications. She was initially treated with an NSAID resulting in complete resolution of her symptoms for three months. After the second recurrence of rash and arthralgias she was referred to Rheumatology for further evaluation. Se- rology revealed a positive ANA, negative AMA, and an alkaline phospha- tase (AP) of 1213. Gastroenterology evaluation included a normal ERCP. A liver biopsy revealed cholangitis with piecemeal necrosis and expanding portal fibrosis (stage III/IV). Biopsy of her lower extremity rash was consistent with lymphocytic vasculitis. Treatment was initiated with cor- ticosteroids and ursodeoxycholic acid (URSO), which resulted in marked resolution of her rash and normalization of her AP. Discussion: Autoimmune cholangitis is a chronic cholestatic hepatitis characterized by the presence of antinuclear antibodies, the absence of antimitochondrial antibodies, and features of destructive cholangitis on histologic examination. We have not seen a case presenting as a cutaneous lymphocytic vasculitis. 274 THE EFFECT OF SILYBUM MARIANUM ON THE VIRAL LOAD OF HISPANIC PATIENTS WITH CHRONIC HEPATITIS C Federico Rodriguez–Perez, M.D., Federico Rodriguez–Serrano and Doris Toro, M.D.*. Gastroenterology, VA Medical Center, San Juan, Puerto Rico.,/OTHER-AFF Purpose: Hepatitis C virus causes liver inflammation and damage through oxidative stress and immune mechanisms. Silybum marianum is a natural herb that protects against oxidative stress and tissue damage.This is a case– control study to assess the response to Silybum marianum in patients with HVC by measuring the viral load and liver enzymes (AST and ALT) before and after a one month therapy. Methods: 17 subjects with HCV received a dose of 160 mg (80% of 200 mg softgel capsule) three times a day for four weeks and a control group of 17 patients with HCV with no treatment. None of the patients were on antiviral therapy or had been for the previous six months. All had com- pensated liver disease. The hepatitis C viral load, AST, and ALT were measured at baseline and after the one–month period. Paired t test and Mann–Whitney test were used for statistical analysis. Results: There were no significant demographic differences between the two groups. The mean age among treated subjects was 49.2 and 50.7 for the control group. After comparing baseline and week 4 levels, a p–value of 0.6 was observed for AST (85.2 vs. 82.6 IU/mL), p–value of 0.58 for ALT (120.4 vs. 116.4 IU/mL), and a p–value of 0.83 for the viral load (8.8 x 10 vs. 8.5 x 10 IU/mL). Among the control group, a p–value of 0.005 was observed for AST level (70.9 vs. 93.9 IU/mL), p–value of 0.049 for ALT (97.4 vs. 114.4 IU/mL), and a p–value of 0.005 for the viral load (1.8 x 10 6 vs. 4.9 x 10 6 IU/mL). The Mann–Whitney test was employed to compare the percent of change from baseline to week four between treated and untreated patient. A significant change was observed for AST (p0.017) and ALT (p0.0152). Nevertheless, the percent change for viral load levels was not statistically significant (p0.063). Conclusions: These results strongly suggest that Silybum marianum may have a protective effect in the inflammatory response to the Hepatitis C virus as observed by a lack of increase in the liver enzymes in the subjects taking this natural herb. This effect probably results from its activity as an antioxidant agent. The effect on viral load, even when present, was less significant possibly because Silybum marianum has less or no efficacy as an antiviral agent. 275 IMMUNE ALTERATIONS AND PROFILE OF LYMPHOCYTE SUBSETS IN TREATMENT RESISTANT CHRONIC HEPATITIS C PATIENTS, AFTER PEG–INTERFERON RIBAVIRIN COMBINATION THERAPY Guilherme Macedo, M.D., FACG*, Susana Lopes, M.D., Joao Pedro Ramos, M.D., Fernando Araujo, M.D. and Fernando Tavarela Veloso, M.D.,Ph.D.,FACG. Gastroenterology Unit, H.S.Joa ˜o, Porto, Portugal. Purpose: Interferon (INF) and Ribavirin (RBV) seem to have different pathophysiological mechanisms in chronic hepatitis C, related to their antiviral and immunomodulation properties. We anaysed the effect of this dual therapy, with PEG–INF RBV in the immune system of treatment resistant HCV patients. Methods: In 30 chronic hepatitis C patients, we evaluated at baseline and week 24, the following immune parameters: complement, immunoglobu- lins, autoantibodies (nuclear, DNA, thyroid, smooth muscle, mithocondrial, platelets). With flux cytometry, we determined the presence of the follow- ing surface antigens, with monoclonal antibodies: CD2, CD3, CD3/CD8, CD3/CD16/CD56, CD8, CD8/CD57, CD16/CD56, CD4/CD45 RA, CD57, CD19, CD29, CD45 RA. Results: There was no significant variation on the prevalence of the studied autoantibodies. There was no evidence of increased expression of lympho- cyte activation markers. Conclusions: Combined therapy of PEG–INFRBV did not induce any significative modification in the immune parameters, and were not corre- lated with the observed increased efficacy of this treatment. 276 A REPORT ON HEPATOCELLULAR CANCER SCREENING IN A LARGE TERTIARY CARE HEPATITIS C CLINIC Vajravel M. Prasad, M.D., Asif Husain, M.D., Linda Reed, N.P. and T. Ulf Westblom, M.D.*. Department of Medicine, VA Medical Center/ Texas A&M University College of Medicine, Temple, TX. Purpose: Surveillance for Hepatocellular carcinoma (HCC) in patients with long standing chronic hepatitis C with Ultrasonography (US) and Alpha–fetoprotein (AFP) determination is a recommended practice. Ca- turelli et al (Am J Gastroenterol 2002;97:397– 405) have reported that only 51 of the 269 patients (19%) with HCC had AFP elevations above 200 ng/ml. The purpose of this study was to assess the HCC screening in a large tertiary care Hepatitis C clinic. Methods: A dedicated hepatitis C clinic was set up in February 2000 at the VA Medical Center. A standardized protocol was used, which included performing US liver and AFP determinations on all chronic hepatitis C patients on enrollment. An analysis of the incidence, ETOH use, risk factors, cirrhosis and associated AFP levels in patients with HCC were performed. Results: 1356 patients were seen from February 2000 to April 2002. Seven out of 1356 patients (0.52 %) had HCC. Only 2 out of the 7 patients (28.6%) had AFP elevated above 50 ng/ml. The diagnosis of HCC was confirmed in 6 out of 7 patients by CT guided biopsy and/or by surgical pathology. The patient #7 did not have histological confirmation, but was referred to radio frequency ablation based on AFP of 1450 ng/ml. Heavy ETOH use was present in 6 out of 7 patients with HCC. The characteristics of the seven patients with HCC are given in the table. S90 Abstracts AJG – Vol. 97, No. 9, Suppl., 2002
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Transcript of Immune alterations and profile of lymphocyte subsets in treatment resistant chronic hepatitis C...
273
AUTOIMMUNE CHOLANGITIS MANIFESTING ASCUTANEOUS LYMPHOCYTIC VASCULITIS OF THE LOWEREXTREMITIESAlex R. Rusynyk, D.O., Michael J. Komar, M.D.* and Matthew B.Grundfast, D.O. Gastroenterology and Nutrition, Geisinger MedicalCenter, Danville, PA.
Background: Autoimmune cholangitis is a rare disorder in which patientsexhibit histologic features suggesting primary biliary cirrhosis, but areoften seronegative for antimitochondrial antibody (AMA), and tend to havecirculating antinuclear antibodies (ANA). We report a case of autoimmunecholangitis diagnosed in a 43–year–old female with a recurrent lowerextremity rash.Case Report: A 43–year–old white female presented to her PCP with abilateral lower extremity erythematous rash and arthralgias. Her past med-ical history was unremarkable, and she was not taking any medications. Shewas initially treated with an NSAID resulting in complete resolution of hersymptoms for three months. After the second recurrence of rash andarthralgias she was referred to Rheumatology for further evaluation. Se-rology revealed a positive ANA, negative AMA, and an alkaline phospha-tase (AP) of 1213. Gastroenterology evaluation included a normal ERCP.A liver biopsy revealed cholangitis with piecemeal necrosis and expandingportal fibrosis (stage III/IV). Biopsy of her lower extremity rash wasconsistent with lymphocytic vasculitis. Treatment was initiated with cor-ticosteroids and ursodeoxycholic acid (URSO), which resulted in markedresolution of her rash and normalization of her AP.Discussion: Autoimmune cholangitis is a chronic cholestatic hepatitischaracterized by the presence of antinuclear antibodies, the absence ofantimitochondrial antibodies, and features of destructive cholangitis onhistologic examination. We have not seen a case presenting as a cutaneouslymphocytic vasculitis.
274
THE EFFECT OF SILYBUM MARIANUM ON THE VIRALLOAD OF HISPANIC PATIENTS WITH CHRONIC HEPATITISCFederico Rodriguez–Perez, M.D., Federico Rodriguez–Serrano andDoris Toro, M.D.*. Gastroenterology, VA Medical Center, San Juan,Puerto Rico.,/OTHER-AFF
Purpose: Hepatitis C virus causes liver inflammation and damage throughoxidative stress and immune mechanisms. Silybum marianum is a naturalherb that protects against oxidative stress and tissue damage.This is acase–control study to assess the response to Silybum marianum in patientswith HVC by measuring the viral load and liver enzymes (AST and ALT)before and after a one month therapy.Methods: 17 subjects with HCV received a dose of 160 mg (80% of 200mg softgel capsule) three times a day for four weeks and a control groupof 17 patients with HCV with no treatment. None of the patients were onantiviral therapy or had been for the previous six months. All had com-pensated liver disease. The hepatitis C viral load, AST, and ALT weremeasured at baseline and after the one–month period. Paired t test andMann–Whitney test were used for statistical analysis.Results: There were no significant demographic differences between thetwo groups. The mean age among treated subjects was 49.2 and 50.7 for thecontrol group. After comparing baseline and week 4 levels, a p–value of 0.6was observed for AST (85.2 vs. 82.6 IU/mL), p–value of 0.58 for ALT(120.4 vs. 116.4 IU/mL), and a p–value of 0.83 for the viral load (8.8 x 10vs. 8.5 x 10 IU/mL). Among the control group, a p–value of 0.005 wasobserved for AST level (70.9 vs. 93.9 IU/mL), p–value of 0.049 for ALT(97.4 vs. 114.4 IU/mL), and a p–value of 0.005 for the viral load (1.8 x 106
vs. 4.9 x 106 IU/mL). The Mann–Whitney test was employed to comparethe percent of change from baseline to week four between treated anduntreated patient. A significant change was observed for AST (p�0.017)
and ALT (p�0.0152). Nevertheless, the percent change for viral load levelswas not statistically significant (p�0.063).Conclusions: These results strongly suggest that Silybum marianum mayhave a protective effect in the inflammatory response to the Hepatitis Cvirus as observed by a lack of increase in the liver enzymes in the subjectstaking this natural herb. This effect probably results from its activity as anantioxidant agent. The effect on viral load, even when present, was lesssignificant possibly because Silybum marianum has less or no efficacy as anantiviral agent.
275
IMMUNE ALTERATIONS AND PROFILE OF LYMPHOCYTESUBSETS IN TREATMENT RESISTANT CHRONIC HEPATITISC PATIENTS, AFTER PEG–INTERFERON � RIBAVIRINCOMBINATION THERAPYGuilherme Macedo, M.D., FACG*, Susana Lopes, M.D., Joao PedroRamos, M.D., Fernando Araujo, M.D. and Fernando Tavarela Veloso,M.D.,Ph.D.,FACG. Gastroenterology Unit, H.S.Joao, Porto, Portugal.
Purpose: Interferon (INF) and Ribavirin (RBV) seem to have differentpathophysiological mechanisms in chronic hepatitis C, related to theirantiviral and immunomodulation properties.
We anaysed the effect of this dual therapy, with PEG–INF � RBV in theimmune system of treatment resistant HCV patients.Methods: In 30 chronic hepatitis C patients, we evaluated at baseline andweek 24, the following immune parameters: complement, immunoglobu-lins, autoantibodies (nuclear, DNA, thyroid, smooth muscle, mithocondrial,platelets). With flux cytometry, we determined the presence of the follow-ing surface antigens, with monoclonal antibodies: CD2, CD3, CD3/CD8,CD3/CD16/CD56, CD8, CD8/CD57, CD16/CD56, CD4/CD45 RA, CD57,CD19, CD29, CD45 RA.Results: There was no significant variation on the prevalence of the studiedautoantibodies. There was no evidence of increased expression of lympho-cyte activation markers.Conclusions: Combined therapy of PEG–INF�RBV did not induce anysignificative modification in the immune parameters, and were not corre-lated with the observed increased efficacy of this treatment.
276
A REPORT ON HEPATOCELLULAR CANCER SCREENING INA LARGE TERTIARY CARE HEPATITIS C CLINICVajravel M. Prasad, M.D., Asif Husain, M.D., Linda Reed, N.P. and T.Ulf Westblom, M.D.*. Department of Medicine, VA Medical Center/Texas A&M University College of Medicine, Temple, TX.
Purpose: Surveillance for Hepatocellular carcinoma (HCC) in patientswith long standing chronic hepatitis C with Ultrasonography (US) andAlpha–fetoprotein (AFP) determination is a recommended practice. Ca-turelli et al (Am J Gastroenterol 2002;97:397–405) have reported that only51 of the 269 patients (19%) with HCC had AFP elevations above 200ng/ml. The purpose of this study was to assess the HCC screening in a largetertiary care Hepatitis C clinic.Methods: A dedicated hepatitis C clinic was set up in February 2000 at theVA Medical Center. A standardized protocol was used, which includedperforming US liver and AFP determinations on all chronic hepatitis Cpatients on enrollment. An analysis of the incidence, ETOH use, riskfactors, cirrhosis and associated AFP levels in patients with HCC wereperformed.Results: 1356 patients were seen from February 2000 to April 2002. Sevenout of 1356 patients (0.52 %) had HCC. Only 2 out of the 7 patients(28.6%) had AFP elevated above 50 ng/ml. The diagnosis of HCC wasconfirmed in 6 out of 7 patients by CT guided biopsy and/or by surgicalpathology. The patient #7 did not have histological confirmation, but wasreferred to radio frequency ablation based on AFP of 1450 ng/ml. HeavyETOH use was present in 6 out of 7 patients with HCC. The characteristicsof the seven patients with HCC are given in the table.
S90 Abstracts AJG – Vol. 97, No. 9, Suppl., 2002
