pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis c after liver...

1
73.9%–79.3% and 64.7%– 65.9% respectively. There was no statistically significant difference between two groups (p0.05). Similarly, 1 month, 1, 5, 10 year graft survival among mismatched and identical groups were 87%–96%, 83.2%– 89%, 71.3%–78.3%, 58.8%– 65.6% respectively. Al- though graft survival is less in mismatched group than the compatible groups this difference were not statistically significant (p0.05). All of the patients in mismatched group were in high UNOS status for listing. There was only 1 incompatible mismatch (B to A) who developed primary non-function. Conclusions: Our results shows that, there was no statistically significant difference in graft and patient survival among ABO compatible mis- matched and identical groups. Nevertheless, ABO compatible mismatched transplantations are still unavoidable in the face of the organ shortage. This type of transplantation can be safely performed, especially among patients with high UNOS listing status. 287 COLCHICINE: AN UNUSUAL CAUSE OF ACUTE HEPATITIS Manjushree Gautam, Tasbirul Islam, Naushad Shaikh, Shailender Singh*. Mercy Catholic Medical Center, Philadephia, PA. Purpose: A 32-year-old male with past medical history of chronic renal failure and gout was admitted for an episode of acute oligo-articular arthritis involving both knee joints and right ankle joint. Review of systems was unremarkable. His only medication was ibuprofen for arthritis. There was no history of alcohol use. General physical examination revealed normal vitals. The involved joints were inflamed and tender. Arthrocentesis revealed joint fluid positive for urate crystals. Metabolic panel revealed elevated serum creatinine of 4.1 mg%, normal liver panel with AST of 17 (n14 – 48U/L), ALT of 10 (n7–58U/L), alkaline phosphatase of 92 (n42–157 U/L) and bilirubin of 0.7 (n0.4 –1.4mg/dl). He was started on colchicine and steroids with marked improvement in symptoms. After receiving a total of 2 mg of colchicine, patient developed gastrointestinal toxicity in the form of nausea, vomiting and diarrhea. Repeat blood chem- istry revealed normal complete blood count and coagulation profile. How- ever, liver function tests revealed elevated transaminases (AST 3500 U/L, ALT 1802 U/L) with normal serum bilirubin and alkaline phospha- tase levels. Serum acetaminophen levels were undetectable. Serology for viral hepatitis was negative. In view of cumulative dose of 2 mg and gastrointestinal symptoms in a patient with underlying renal failure col- chicine toxicity was presumed to be the cause of elevated liver transami- nases. Colchicine was discontinued and gradually transaminases returned to normal. Temporal relationship of liver function abnormalities and their improvement on cessation of colchicine implicates colchicine for these abnormalities. Discussion: Colchicine, an alkaloid of the Colchicum species, has anti- inflammatory action in acute gout and has a prophylactic effect against recurrent attacks. It is partially metabolized in liver, with the unchanged drug and metabolites excreted into urine, bile, and feces. Renal impairment is a well-recognized risk factor for colchicine toxicity and warrants upto 50% reduction in colchicine dose. To our knowledge, this is the first report of isolated acute hepatitis occurring with therapeutic dose of colchicine. Although gastrointestinal side effects like nausea and vomiting commonly develop during colchicine therapy, liver panel should be done, as there may be development of acute hepatic injury that would warrant discontinuation of colchicine therapy. 288 MICROSATELLITE INSTABILITY IN HEPATOCELLULAR CARCINOMAS FROM TWO DIFFERENT GEOGRAPHIC REGIONS (PORTUGAL AND MOZAMBIQUE) Jose ´ Alexandre Sarmento, M.D., Jose ´ Ferro, M.D., Carmo Santos, M.D., Raquel Seruca, M.D., Fa ´tima Carneiro, M.D.*. Medical Faculty, Porto, Portugal and Universidade do Porto, Porto, Portugal. Aim: To evaluate the occurence of microsatellite instability (MI) in hep- atocellular carcinomas (HCC), from two different geographic regions- Portugal and Mozambique-known to be countries of intermediate (6 –11 cases /100 000 /year) and very high incidence (30 –150 cases /100 000/ year) of HCC. Material and Methods: We studied 37 cases of HCC: Portugal (n18) and Mozambique (n19). Microsatellite instability was evaluated by the analysis of marker BAT 26, using polymerase chain reaction and electro- phoresis. Immunohistochemical study was performed to estimate the ex- pression of antigens of hepatitis B. Results: In both groups there was a male predominance - M/W8 and M/W2.2, in Portuguese cases and Mozambican series, respectively. The mean age of patients from Mozambique (40.615.7 years) was significan- ltly lower than that of Portuguese patients (65.97.4) (p0.0001). MI was identified in 5/19 (26,3%) HCCs from Mozambique, and in none of the HCCs from Portugal (p0.02). Antigens of HBV were detected in the liver tissue adjacent to HCCs in 32% and 11% of the cases (Mozambique and Portugal respectively). Conclusions: These results show a significant difference between the occurance of MI in HCCs from Portugal and Mozambique. It is tempting to suggest that the occurance of MI in the series from Mozambique may be related with the etiologic factors that are the most important in that area: HBV infection and/or aflatoxins. 289 PILOT STUDY OF PEGYLATED INTERFERON ALFA-2B AND RIBAVIRIN FOR RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION Sandeep Mukherjee, M.D.*, Richard K. Gilroy, M.D., Joyce Rogge, R.N., Lynne Weaver, R.N., Timothy M. McCashland, M.D., Daniel F. Schafer, M.D. University of Nebraska Medical Center, Omaha, NE. Purpose: Background: Recurrent hepatitis C is often treated with inter- feron and ribavirin (Schering-Plough, Kenilworth, NJ,USA) combination therapy but results have been disappointing. Given the promising results reported with pegylated-interferon and ribavirin for hepatitis C, we were interested in evaluating the effectiveness of this treatment in liver transplant recipients with recurrent HCV. Methods: Between November 2001 and September 2002, patients with recurrent HCV were screened to determine if they were eligible for treat- ment. Liver function tests, HCV-RNA and liver biopsies were done on all patients prior to treatment. HCV-RNA was repeated at three months, end of treatment (EOT) and six months after EOT for patients HCV-RNA negative at EOT. Patients were prospectively followed after starting weekly pegylated interferon alfa-2b 1.5mcg/kg per week and ribavirin 800mg per day (Schering-Plough, Kenilworth, NJ,USA) with folic acid 1mg per day. Results: 39 patients were eligible for treatment with a median age of 50.4 years. 18 patients have completed treatment, 4 remain on treatment and 17 were intolerant. Sustained HCVRNA eradication occurred in 66.7% of patients who completed treatment. Side effects led to treatment withdrawal in 17 patients (43.6%) In an intention-to treat analysis, sustained HCVRNA eradication occurred in 30.8% of patients. Conclusions: Side effects are an important limiting factor in the treatment of recurrent HCV with pegylated interferon and ribavirin. However, these results are encouraging as sustained HCV eradication occurred in at least 66.7% of patients who completed treatment. Prospective randomized trials are required to assess the effectiveness of this treatment and its impact on quality of life and histology. S98 Abstracts AJG – Vol. 98, No. 9, Suppl., 2003

Upload: sandeep-mukherjee

Post on 30-Nov-2016

212 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation

73.9%–79.3% and 64.7%–65.9% respectively. There was no statisticallysignificant difference between two groups (p�0.05). Similarly, 1 month, 1,5, 10 year graft survival among mismatched and identical groups were87%–96%, 83.2%–89%, 71.3%–78.3%, 58.8%–65.6% respectively. Al-though graft survival is less in mismatched group than the compatiblegroups this difference were not statistically significant (p�0.05). All of thepatients in mismatched group were in high UNOS status for listing. Therewas only 1 incompatible mismatch (B to A) who developed primarynon-function.Conclusions: Our results shows that, there was no statistically significantdifference in graft and patient survival among ABO compatible mis-matched and identical groups. Nevertheless, ABO compatible mismatchedtransplantations are still unavoidable in the face of the organ shortage. Thistype of transplantation can be safely performed, especially among patientswith high UNOS listing status.

287

COLCHICINE: AN UNUSUAL CAUSE OF ACUTE HEPATITISManjushree Gautam, Tasbirul Islam, Naushad Shaikh,Shailender Singh*. Mercy Catholic Medical Center, Philadephia, PA.

Purpose: A 32-year-old male with past medical history of chronic renalfailure and gout was admitted for an episode of acute oligo-articulararthritis involving both knee joints and right ankle joint. Review of systemswas unremarkable. His only medication was ibuprofen for arthritis. Therewas no history of alcohol use. General physical examination revealednormal vitals. The involved joints were inflamed and tender. Arthrocentesisrevealed joint fluid positive for urate crystals. Metabolic panel revealedelevated serum creatinine of 4.1 mg%, normal liver panel with AST of 17(n�14–48U/L), ALT of 10 (n�7–58U/L), alkaline phosphatase of 92(n�42–157 U/L) and bilirubin of 0.7 (n�0.4–1.4mg/dl). He was started oncolchicine and steroids with marked improvement in symptoms. Afterreceiving a total of 2 mg of colchicine, patient developed gastrointestinaltoxicity in the form of nausea, vomiting and diarrhea. Repeat blood chem-istry revealed normal complete blood count and coagulation profile. How-ever, liver function tests revealed elevated transaminases (AST� 3500U/L, ALT� 1802 U/L) with normal serum bilirubin and alkaline phospha-tase levels. Serum acetaminophen levels were undetectable. Serology forviral hepatitis was negative. In view of cumulative dose of 2 mg andgastrointestinal symptoms in a patient with underlying renal failure col-chicine toxicity was presumed to be the cause of elevated liver transami-nases. Colchicine was discontinued and gradually transaminases returnedto normal. Temporal relationship of liver function abnormalities and theirimprovement on cessation of colchicine implicates colchicine for theseabnormalities.Discussion: Colchicine, an alkaloid of the Colchicum species, has anti-inflammatory action in acute gout and has a prophylactic effect againstrecurrent attacks. It is partially metabolized in liver, with the unchangeddrug and metabolites excreted into urine, bile, and feces. Renal impairmentis a well-recognized risk factor for colchicine toxicity and warrants upto50% reduction in colchicine dose. To our knowledge, this is the first reportof isolated acute hepatitis occurring with therapeutic dose of colchicine.Although gastrointestinal side effects like nausea and vomiting commonlydevelop during colchicine therapy, liver panel should be done, as there maybe development of acute hepatic injury that would warrant discontinuationof colchicine therapy.

288

MICROSATELLITE INSTABILITY IN HEPATOCELLULARCARCINOMAS FROM TWO DIFFERENT GEOGRAPHICREGIONS (PORTUGAL AND MOZAMBIQUE)Jose Alexandre Sarmento, M.D., Jose Ferro, M.D., Carmo Santos, M.D.,Raquel Seruca, M.D., Fatima Carneiro, M.D.*. Medical Faculty, Porto,Portugal and Universidade do Porto, Porto, Portugal.

Aim: To evaluate the occurence of microsatellite instability (MI) in hep-atocellular carcinomas (HCC), from two different geographic regions-Portugal and Mozambique-known to be countries of intermediate (6–11cases /100 000 /year) and very high incidence (30–150 cases /100 000/year) of HCC.Material and Methods: We studied 37 cases of HCC: Portugal (n�18)and Mozambique (n�19). Microsatellite instability was evaluated by theanalysis of marker BAT 26, using polymerase chain reaction and electro-phoresis. Immunohistochemical study was performed to estimate the ex-pression of antigens of hepatitis B.Results: In both groups there was a male predominance - M/W�8 andM/W�2.2, in Portuguese cases and Mozambican series, respectively. Themean age of patients from Mozambique (40.6�15.7 years) was significan-ltly lower than that of Portuguese patients (65.9�7.4) (p�0.0001). MI wasidentified in 5/19 (26,3%) HCCs from Mozambique, and in none of theHCCs from Portugal (p�0.02). Antigens of HBV were detected in the livertissue adjacent to HCCs in 32% and 11% of the cases (Mozambique andPortugal respectively).Conclusions: These results show a significant difference between theoccurance of MI in HCCs from Portugal and Mozambique. It is temptingto suggest that the occurance of MI in the series from Mozambique may berelated with the etiologic factors that are the most important in that area:HBV infection and/or aflatoxins.

289

PILOT STUDY OF PEGYLATED INTERFERON ALFA-2B ANDRIBAVIRIN FOR RECURRENT HEPATITIS C AFTER LIVERTRANSPLANTATIONSandeep Mukherjee, M.D.*, Richard K. Gilroy, M.D.,Joyce Rogge, R.N., Lynne Weaver, R.N., Timothy M. McCashland, M.D.,Daniel F. Schafer, M.D. University of Nebraska Medical Center,Omaha, NE.

Purpose: Background: Recurrent hepatitis C is often treated with inter-feron and ribavirin (Schering-Plough, Kenilworth, NJ,USA) combinationtherapy but results have been disappointing. Given the promising resultsreported with pegylated-interferon and ribavirin for hepatitis C, we wereinterested in evaluating the effectiveness of this treatment in liver transplantrecipients with recurrent HCV.Methods: Between November 2001 and September 2002, patients withrecurrent HCV were screened to determine if they were eligible for treat-ment. Liver function tests, HCV-RNA and liver biopsies were done on allpatients prior to treatment. HCV-RNA was repeated at three months, endof treatment (EOT) and six months after EOT for patients HCV-RNAnegative at EOT. Patients were prospectively followed after starting weeklypegylated interferon alfa-2b 1.5mcg/kg per week and ribavirin 800mg perday (Schering-Plough, Kenilworth, NJ,USA) with folic acid 1mg per day.Results: 39 patients were eligible for treatment with a median age of 50.4years. 18 patients have completed treatment, 4 remain on treatment and 17were intolerant. Sustained HCVRNA eradication occurred in 66.7% ofpatients who completed treatment. Side effects led to treatment withdrawalin 17 patients (43.6%) In an intention-to treat analysis, sustained HCVRNAeradication occurred in 30.8% of patients.Conclusions: Side effects are an important limiting factor in the treatmentof recurrent HCV with pegylated interferon and ribavirin. However, theseresults are encouraging as sustained HCV eradication occurred in at least66.7% of patients who completed treatment. Prospective randomized trialsare required to assess the effectiveness of this treatment and its impact onquality of life and histology.

S98 Abstracts AJG – Vol. 98, No. 9, Suppl., 2003