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Thombocytopenia (T) in patients with chronic hepatitis C: management with interleukin-11 (IL11)
S82
Abstracts
238 SIGNIFICANT PERCENTAGE OF NORMAL ALT VALUES SEEN IN CHRONIC HCV INFECTED PATIENTS AT A VA MEDICAL CENTER Venkat Rangaraj, M.D., Charles Mendenhall, M.D.*, Stephen Goldberg, M.D. The Jewish Hospital of Cincinnati, Cincinnati, OH and The VA Hospital of Cincinnati, Cincinnati, OH. Purpose: Some have proposed that a normal ALT indicates minimal or no liver injury. This study was undertaken to clarify the significance of normal ALT in veterans with active chronic HCV infection. Methods: Eighty Seven positive outpatients referred for treatment at the VA Medical Center Cincinnati were studied prospectively. Pre-treatment laboratory tests included ALT levels, viral genotypes and HCV-RNA loads. Patients with established disease were treated with interferon alpha 2b or Pegylated interferon alpha 2b in combination with Ribavirin using generally accepted protocols. Serum HCV-RNA levels were obtained at 0, 3, 6, 12 months after initiating treatment and again at 18 months. Pre-treatment liver biopsy to stage the fibrosis was performed on every patient. Patients were also followed closely to detect alcohol consumption; treatment was not initiated on any patient if historical or laboratory evidence of alcohol consumption was observed in the preceding 3 month period. We then compared the following 7 variables (race, age, virology genotype, nutrition, biopsy result and response to treatment) of each of the two clinical groups, (normal vs. elevated ALT levels). Results: From a pool of 87 patients (85 males, 2 females) with chronic HCV entering our treatment program, we identified 29 patients (33.33%) with normal serum ALT (⬍50 IU/L) and 58 patients (66.67%) with ⬎50 IU/L serum ALT at baseline. On liver biopsy, 10 of the 29 patients (34.48%) with normal ALT had cirrhosis or incomplete cirrhosis (stage 2.5 to stage 4). In patients with elevated ALT, the prevalence of cirrhosis/ incomplete cirrhosis was seen in “50% of the population. Differences in histological injury seen on liver biopsy (p⬍0.09) and nutritional status (BMI) (p⬍0.08) showed a trend towards significance (p⬎0.05 ⬍ 0.10). We noticed no significant differences in race, age, virology, or response to therapy (pⱖ0.10). Patients with stage 3 or 4 damage to the liver and a BMI of ⬎25 tended to have higher ALT values. Fisher’s exact test was used to compare the characteristic data. Linear regression analysis however showed a significant linear relationship (p ⫽ 0.05) between ALT and liver fibrosis on biopsies. Conclusions: A normal ALT (0 –50 IU/L) did not preclude more severe liver injury in a significant percent of cases. Therefore, the use of ALT in patients with HCV infection is not a predictable indicator of significant underlying liver disease in a veteran population.
239 THOMBOCYTOPENIA (T) IN PATIENTS WITH CHRONIC HEPATITIS C: MANAGEMENT WITH INTERLEUKIN-11 (IL11) Venkat Rangaraj, M.D., Charles Mendenhall, M.D.*, Goldberg Stephen, M.D. The Jewish Hospital of Cincinnati, Cincinnati, OH and The VA Hospital of Cincinnati, Cincinnati, OH. Purpose: Of the 4 million people infected with HCV in the US it is estimated that treatment is interrupted or prevented in 1 million due to thrombocytopenia. In many instances this is the result of portal hypertension with secondary platelet pooling and destruction in the spleen. Peripheral platelet antibody destruction may also contribute even in the absence of severe liver injury. Once therapy is initiated the process is further exacerbated by bone marrow suppression associated with interferon therapy (IFN). This combination of events may result in life threatening T. Purpose: Describe T in the veteran population and indicate one corrective therapeutic action. Methods: Therapy consisted of interferon alfa 2b ⫹ Ribavirin, standard dosing (SD), 3mU, tiw (IFN 2b std) (N ⫽ 65) and high induction dosing 5mU qw for 6 wks, then SD for 42 weeks (IFN 2b high) (N ⫽25) doses, Pegalated Interferon alfa 2b ⫹ Ribavirin standard weight based dosing
AJG – Vol. 98, No. 9, Suppl., 2003
(PEG IFN 2b) (N ⫽ 58) and pegalated Interferon alfa 2a ⫹ Ribavirin; 180 g qw (PEG IFN 2a) (N ⫽ 10). Results: T (⬍120,000/ul) was observed prior to treatment in 35.9% of 145 patients undergoing therapy for HCV. We noticed a significant decrease in platelets during treatment. Platelet changes from baseline (% decrease) at time 2, 12, 26, 48 weeks were: ⫺4.8%, ⫺10.0%, ⫺7.0%, ⫺9.0% for the IFN 2b std. On IFN 2b high decreases were, ⫺23.7%, ⫺6.1%, ⫹7.4%, ⫺22.6%. On PEG IFN 2b they were ⫺18.2%, ⫺30.0%, ⫺35.7, ⫺27.7%. On IFN 2a they were ⫺27.4%, ⫺38.1%, ⫺23.3%. Of all those patients that had thrombocytopenia 29% (15/52) were sufficiently severe so as to require IL11 to prevent IFN dose reduction or discontinuation and 1.4% (2/145) required IL 11 prior to IFN to raise platelets to recommended safe IFN treatment levels. All patients responded to IL 11. Only side effect observed was fluid accumulation in 13% (2/15) of subjects, which was easily managed with diuretics. Conclusions: T is a common problem before and during HCB therapy with IFN. Management with IL 11 permits continuation of IFN therapy without dose reduction.
240 OCCUPATIONAL EXPOSURE TO HEPATITIS C: HOW 12 HOSPITALS IN NEW YORK CITY MANAGE OCCUPATIONAL EXPOSURE TO HEPATITIS C Prem Chattoo, D.O., David Feldman, M.D.*, James Robilotti, M.D. Saint Vincents Hospital, New York, NY. Purpose: Occupational exposure to Hepatitis C by percutaneous needle stick occurs infrequently. The risk of transmission of Hepatitis C from a single deep needle stick averages 1.8% in prospective studies. The data from the CDC report that 4% of persons testing positive for Hepatitis C acquired it occupationally. The evaluation and management of Acute Hepatitis C acquired occupationally has not been well studied or standardized. Methods: We poled 12 hospitals in New York City (Six University and Six Community Hospitals) for their protocols on Hepatitis C exposure for needle sticks. OSHA mandates evaluation of these cases, but only the CDC has guidelines on the evaluation. No treatment recommendations are available for post exposure prophylaxis or treatment of Acute Hepatitis C. Both HIV and Hepatitis B have treatment strategies to offer exposed health care workers. Results: All of the hospitals offered reasonable testing to their employees exposed to Hepatitis C. None of the hospitals offered any treatment regimen in their protocol. Treatment if any, would be dependent on the opinion of the physician evaluating the patient. Some studies have suggested that earlier treatment may be beneficial. None of the hospital’s knew of the reporting hotline at either the CDC or the possibility of enrolling patients in the NIH trial for Acute Hepatitis C. Acute Hep C Protocol CDC Guideline Baseline Hep C Ab & LFT Hep C PCR baseline Hep C PCR 4-6wks Hep C PCR ⬎ 4wks Hep C Ab 4–6wks Hep C Ab 12wks HepCAb4–6Month Hep C Ab 12 month Refer to Hep Specialist Treatment offered Referral to Study
University Community Hosp UH% Hosp CH%
Recommended
6
100%
6
100%
Not recommended Optional Not recommended Not recommended Not recommended Recommended Not recommended Recommended Unknown Hotline number
0 2 0 0 5 2 2 0 0 0
0% 33% 0% 0% 83% 33% 33% 0% 0% 0%
0 3 0 0 3 2 0 1 0 0
0% 50% 0% 0% 50% 33% 0% 17% 0% 0%
Conclusions: The evaluation of Hepatitis C exposure should be standardized and a recommendation to earlier PCR testing could be beneficial. Options for treatment should be made available to those who test positive.
Abstracts
238 SIGNIFICANT PERCENTAGE OF NORMAL ALT VALUES SEEN IN CHRONIC HCV INFECTED PATIENTS AT A VA MEDICAL CENTER Venkat Rangaraj, M.D., Charles Mendenhall, M.D.*, Stephen Goldberg, M.D. The Jewish Hospital of Cincinnati, Cincinnati, OH and The VA Hospital of Cincinnati, Cincinnati, OH. Purpose: Some have proposed that a normal ALT indicates minimal or no liver injury. This study was undertaken to clarify the significance of normal ALT in veterans with active chronic HCV infection. Methods: Eighty Seven positive outpatients referred for treatment at the VA Medical Center Cincinnati were studied prospectively. Pre-treatment laboratory tests included ALT levels, viral genotypes and HCV-RNA loads. Patients with established disease were treated with interferon alpha 2b or Pegylated interferon alpha 2b in combination with Ribavirin using generally accepted protocols. Serum HCV-RNA levels were obtained at 0, 3, 6, 12 months after initiating treatment and again at 18 months. Pre-treatment liver biopsy to stage the fibrosis was performed on every patient. Patients were also followed closely to detect alcohol consumption; treatment was not initiated on any patient if historical or laboratory evidence of alcohol consumption was observed in the preceding 3 month period. We then compared the following 7 variables (race, age, virology genotype, nutrition, biopsy result and response to treatment) of each of the two clinical groups, (normal vs. elevated ALT levels). Results: From a pool of 87 patients (85 males, 2 females) with chronic HCV entering our treatment program, we identified 29 patients (33.33%) with normal serum ALT (⬍50 IU/L) and 58 patients (66.67%) with ⬎50 IU/L serum ALT at baseline. On liver biopsy, 10 of the 29 patients (34.48%) with normal ALT had cirrhosis or incomplete cirrhosis (stage 2.5 to stage 4). In patients with elevated ALT, the prevalence of cirrhosis/ incomplete cirrhosis was seen in “50% of the population. Differences in histological injury seen on liver biopsy (p⬍0.09) and nutritional status (BMI) (p⬍0.08) showed a trend towards significance (p⬎0.05 ⬍ 0.10). We noticed no significant differences in race, age, virology, or response to therapy (pⱖ0.10). Patients with stage 3 or 4 damage to the liver and a BMI of ⬎25 tended to have higher ALT values. Fisher’s exact test was used to compare the characteristic data. Linear regression analysis however showed a significant linear relationship (p ⫽ 0.05) between ALT and liver fibrosis on biopsies. Conclusions: A normal ALT (0 –50 IU/L) did not preclude more severe liver injury in a significant percent of cases. Therefore, the use of ALT in patients with HCV infection is not a predictable indicator of significant underlying liver disease in a veteran population.
239 THOMBOCYTOPENIA (T) IN PATIENTS WITH CHRONIC HEPATITIS C: MANAGEMENT WITH INTERLEUKIN-11 (IL11) Venkat Rangaraj, M.D., Charles Mendenhall, M.D.*, Goldberg Stephen, M.D. The Jewish Hospital of Cincinnati, Cincinnati, OH and The VA Hospital of Cincinnati, Cincinnati, OH. Purpose: Of the 4 million people infected with HCV in the US it is estimated that treatment is interrupted or prevented in 1 million due to thrombocytopenia. In many instances this is the result of portal hypertension with secondary platelet pooling and destruction in the spleen. Peripheral platelet antibody destruction may also contribute even in the absence of severe liver injury. Once therapy is initiated the process is further exacerbated by bone marrow suppression associated with interferon therapy (IFN). This combination of events may result in life threatening T. Purpose: Describe T in the veteran population and indicate one corrective therapeutic action. Methods: Therapy consisted of interferon alfa 2b ⫹ Ribavirin, standard dosing (SD), 3mU, tiw (IFN 2b std) (N ⫽ 65) and high induction dosing 5mU qw for 6 wks, then SD for 42 weeks (IFN 2b high) (N ⫽25) doses, Pegalated Interferon alfa 2b ⫹ Ribavirin standard weight based dosing
AJG – Vol. 98, No. 9, Suppl., 2003
(PEG IFN 2b) (N ⫽ 58) and pegalated Interferon alfa 2a ⫹ Ribavirin; 180 g qw (PEG IFN 2a) (N ⫽ 10). Results: T (⬍120,000/ul) was observed prior to treatment in 35.9% of 145 patients undergoing therapy for HCV. We noticed a significant decrease in platelets during treatment. Platelet changes from baseline (% decrease) at time 2, 12, 26, 48 weeks were: ⫺4.8%, ⫺10.0%, ⫺7.0%, ⫺9.0% for the IFN 2b std. On IFN 2b high decreases were, ⫺23.7%, ⫺6.1%, ⫹7.4%, ⫺22.6%. On PEG IFN 2b they were ⫺18.2%, ⫺30.0%, ⫺35.7, ⫺27.7%. On IFN 2a they were ⫺27.4%, ⫺38.1%, ⫺23.3%. Of all those patients that had thrombocytopenia 29% (15/52) were sufficiently severe so as to require IL11 to prevent IFN dose reduction or discontinuation and 1.4% (2/145) required IL 11 prior to IFN to raise platelets to recommended safe IFN treatment levels. All patients responded to IL 11. Only side effect observed was fluid accumulation in 13% (2/15) of subjects, which was easily managed with diuretics. Conclusions: T is a common problem before and during HCB therapy with IFN. Management with IL 11 permits continuation of IFN therapy without dose reduction.
240 OCCUPATIONAL EXPOSURE TO HEPATITIS C: HOW 12 HOSPITALS IN NEW YORK CITY MANAGE OCCUPATIONAL EXPOSURE TO HEPATITIS C Prem Chattoo, D.O., David Feldman, M.D.*, James Robilotti, M.D. Saint Vincents Hospital, New York, NY. Purpose: Occupational exposure to Hepatitis C by percutaneous needle stick occurs infrequently. The risk of transmission of Hepatitis C from a single deep needle stick averages 1.8% in prospective studies. The data from the CDC report that 4% of persons testing positive for Hepatitis C acquired it occupationally. The evaluation and management of Acute Hepatitis C acquired occupationally has not been well studied or standardized. Methods: We poled 12 hospitals in New York City (Six University and Six Community Hospitals) for their protocols on Hepatitis C exposure for needle sticks. OSHA mandates evaluation of these cases, but only the CDC has guidelines on the evaluation. No treatment recommendations are available for post exposure prophylaxis or treatment of Acute Hepatitis C. Both HIV and Hepatitis B have treatment strategies to offer exposed health care workers. Results: All of the hospitals offered reasonable testing to their employees exposed to Hepatitis C. None of the hospitals offered any treatment regimen in their protocol. Treatment if any, would be dependent on the opinion of the physician evaluating the patient. Some studies have suggested that earlier treatment may be beneficial. None of the hospital’s knew of the reporting hotline at either the CDC or the possibility of enrolling patients in the NIH trial for Acute Hepatitis C. Acute Hep C Protocol CDC Guideline Baseline Hep C Ab & LFT Hep C PCR baseline Hep C PCR 4-6wks Hep C PCR ⬎ 4wks Hep C Ab 4–6wks Hep C Ab 12wks HepCAb4–6Month Hep C Ab 12 month Refer to Hep Specialist Treatment offered Referral to Study
University Community Hosp UH% Hosp CH%
Recommended
6
100%
6
100%
Not recommended Optional Not recommended Not recommended Not recommended Recommended Not recommended Recommended Unknown Hotline number
0 2 0 0 5 2 2 0 0 0
0% 33% 0% 0% 83% 33% 33% 0% 0% 0%
0 3 0 0 3 2 0 1 0 0
0% 50% 0% 0% 50% 33% 0% 17% 0% 0%
Conclusions: The evaluation of Hepatitis C exposure should be standardized and a recommendation to earlier PCR testing could be beneficial. Options for treatment should be made available to those who test positive.