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The proto-oncogene Akt is expressed in hepatocellular carcinoma: potential target for chemoprevention by sulindac
S124
Abstracts
Also the mean PyNPase level in the metastatic tumor foci was significantly higher than that in normal surrounding tissues (p ⫽ 0.009). Conclusions: PyNPase levels in both primary tumor and metastasized hepatic tumor foci were significantly higher than those in normal surrounding tissues. Therefore, it was suggested that determination of PyNPase levels in various tissue specimens obtained from patients with progressive large bowel cancer metastasized to the liver may aid in predicting the therapeutic effects of treatment with 5⬘-DFUR.
388 Danazol associated hepatic lesions Alaa G. Iskandar, MD, Sandy Gulati, MD, and Abhijit Kulkarni, MD*. 1 Gastroenterology, Allegheny General Hospital, Pittsburgh, PA, United States. Purpose: Anabolic androgenic steroids are commonly used in the treatment of various autoimmune conditions including idiopathic thrombocytopenic purpura (ITP). Case reports have associated danazol with benign as well as malignant hepatic lesions. Danazol is a pituitary gonadotropin antagonist with weak androgenic effects. We report the occurrence of a hepatic lesion consistent with hepatic adenoma in one patient receiving long-term danazol therapy for ITP. Methods: A 76 year old white male with a ten year history of steroid refractory ITP was subsequently placed on Danazol. After five years of therapy, a CT scan was obtained to evaluate nephrolithiasis, during which time an incidental 6 cm lesion was seen in the right hepatic lobe. A biopsy of this lesion was precluded due to its peridiaphragmatic location. A year later, the patient presented to the ER with a 48 hour history of sharp intermittent RUQ pain. Physical examination was significant for tender hepatomegaly. CT scan revealed an increase in the size of the previously found hepatic lesion to 12 cm and was associated with hemorrhage. In lieu of the above findings, the patient underwent a mesenteric angiogram which revealed bleeding arising from the right inferior and left hepatic arteries. A mass like lesion was seen fed by both vessels. Gelfoam embolization was successfully performed. Three months later, a follow up MRI of liver with gadolinium showed a reduction in size of the hepatic lesion. AFP and CEA were persistently normal. Results: The differential diagnosis of this lesion includes hepatic adenoma, hemangioma, focal nodular hyperplasia, hepatocellular carcinoma and metastatic disease. The combination of clinical history and radiographic findings in this patient suggested a hepatic adenoma, particularly in view of long term Danazol use. This patient’s hepatic lesion is consistent with the typical features seen in adenoma: rapid growth, large size and intratumor hemorrhage. The sudden onset of RUQ pain by our patient was most likely due to the extensive hemorrhage into the tumor. Hepatocellular adenomas are benign lesions with a prevalence of 3/100,000. They have been observed in women taking oral contraceptives and are associated with the use of anabolic steroids. They occur mainly in the right lobe of the liver. Treatment of hepatic adenomas should include cessation of steroids since it causes shrinkage or resolution of the hepatic tumors. Surgery is reserved for symptomatic patients. Conclusions: Benign hepatic lesions may be seen in patients on long term anabolic steroid therapy. Serial ultrasonography should be performed in these patients.
389 Our experience with percutaneous liver biopsy performed under IV propofol sedation Thirumalesh P Kanchana1, Shivakumar Vignesh1, Vivek Kaul1, Surakit Pungpapong2, Kenneth D Rothstein3 and Santiago J Munoz3*. 1 Gastroenterology; 2Medicine; and 3Hepatology, Albert Einstein Medical Center, Philadelphia, PA, United States. Purpose: Percutaneous liver biopsy (LB) for the diagnosis of liver disease is a well-established and routinely used procedure. Because of the necessity
AJG – Vol. 96, No. 9, Suppl., 2001
for the patient to cooperate with breath holding during the procedure, LB is performed by most physicians without any pre-procedure sedation. However, it is invasive and often patients have significant pain and anxiety. Propofol (PFL) is an anesthetic agent, which has been used for induction and maintenance of anesthesia as well as for sedation. PFL by continuous infusion provides a readily titratable level of sedation and a rapid recovery once infusion is terminated. In comparison with midazolam when used to maintain sedation, PFL provides equal or better control and more rapid recovery. Even though there are some published data regarding the midazolam sedation for LB, there is no data published in the literature to-date regarding the use of IV PFL for LB. Methods: Data from all the patients who underwent LB in our institution by one of the authors during two years from 10/98 to 10/00 were reviewed. All LB done under IV PFL sedation during this period were analyzed. Out of 81 patients who had undergone LBs during this period, 49 patients had had IV PFL sedation based on their preference. All the patients received PFL by anesthesiologist and were observed till complete recovery. Results: Patients were between 19 to 55 years of age (mean 43.8). 36 patients were males (73.5%) and 13 (26.5%) were females. 44 patients had Hepatitis C (89.8%), 3 had chronic hepatitis, 1 autoimmune hepatitis, and another patient had NASH. Two patients with Hepatitis C also were positive for HIV infection and 1 patient with Hepatitis C also had coinfection with Hepatitis B. All the patients recovered from the sedation rapidly and were discharged the same day of LB. However, one patient was readmitted the next day with pain. The average size of the specimen was14.1 mm (range 4 –30 mm) and the pathologists were able to make an accurate diagnosis in all cases. Conclusions: PFL sedation can be used successfully in patients undergoing liver LB. Patients can be sedated completely and LB can be obtained with no anxiety or pain. All the patients tolerated the procedure well. LB was done successfully in all the patients with adequate tissue samples. Although none of the patients in this study had major complications, a much larger study using PFL for LB is needed to assess the complication rate. IV PFL sedation can be especially helpful in highly anxious or uncooperative patients and who may need multiple LBs due to their chronic liver disease.
390 The proto-oncogene Akt is expressed in hepatocellular carcinoma: potential target for chemoprevention by sulindac William J Karolski1, Rodney M Markin2, Timothy M McCashland1 and Hemant K Roy1*. 1Internal Medicine, University of Nebraksa Medical Center, Omaha, Nebraska, United States; and 2Pathology, University of Nebraska Medical Center, Omaha, Nebraska, United States. Purpose: The mortality from hepatocellular carcinoma (HCC) in this country is rapidly rising, underscoring the need for chemoprevention. Nonsteroidal antiinflammatory drugs (NSAIDS) have been demonstrated to prevent GI malignancies through both cyclooxygenase (COX)2-dependent and -independent mechanisms. COX 2 has been demonstrated to be overexpressed in HCC, but only in the subset of well-differentiated tumors. The proto-oncogene Akt has recently been demonstrated to be a NSAID target. This serine-threonine kinase has a myriad of potentially neoplastic actions including increasing cellular proliferation, inhibiting apoptosis and stimulating angiogenesis. Therefore, we wanted to evaluate Akt expression in HCC and determine if NSAIDs would modulate expression and/or activity in human HCC cell lines. Methods: Immunohistochemistry was performed on 26 HCC with a polyclonal antibody to Akt 1/2. Slides were developed with a Vectastain ABC kit. Two human HCC cell lines (HepG2 and HuH7) that have different molecular genetic characteristics were treated for 5 days with either sulindac 800 M or vehicle. Cell counts were obtained. Following, cell lysates were made and subjected to immunoblot analysis using a polyclonal antibody to Akt 1/2, serine-473 phosphorylated Akt (the activated form) or PARP (a marker of apoptosis). Xerograms were developed with enhanced chemiluminescence and quantitated by laser densitometry.
AJG – September, Suppl., 2001
Results: Akt was detectable in all human HCC. Importantly, Akt was also seen in the surrounding hepatocytes, implying that Akt expression occurs early during carcinogenesis. In cell culture, sulindac treatment resulted in an approximate decrease in cell number by one-half, with a concomitant increase in PARP degradation, suggesting an induction of apoptosis. In HepG2 and HuH7 cell lysates, Akt expression decreased to 75.7 ⫾ 2.9% and 75.8 ⫾ 3.3% of vehicle, respectively (both p ⬍ 0.001). Moreover, the activated Akt form was decreased to 79 ⫾ 5% and 59 ⫾ 4% (p ⬍ 0.001) of vehicle in the Hepg2 and HuH7 cell lines, respectively. Conclusions: We confirm that sulindac may be effective against HCC by inducing apoptosis. Furthermore, our data indicates that Akt is a potential target in that it is expressed in HCC and is both downregulated and inactivated by sulindac. This data provides further support for the use of NSAIDS as a chemopreventive agent against HCC.
391 Impact of psychology evaluation clinic on Rebetron therapy in highrisk mental health patients Gayle Kelsey, Psy.D.1, Daniel Feld, M.A.1, Marna T. Abarientos1 and Ayse Aytaman, M.D.1*. 1Gastroenterology, VA NY Harbor HCS Brooklyn Campus, Brooklyn, New York, United States. Purpose: Patients with chronic hepatitis C infection who have a major affective disorder, as classified by the Diagnostic and Statistical Manual– Fourth Edition (DSM-IV), and a significant history of suicidal or homicidal ideation are not treated with combination therapy (interferon alpha 2B/ ribavirin) because of the risk of severe psychiatric side effects that often arise with treatment. Most United States veterans infected with hepatitis C virus (HCV) are Vietnam-era veterans with significant psychiatric comorbidities that would normally exclude them from therapy. This report will illustrate the successful completion of treatment with Rebetron in two veterans with significant psychiatric comorbidities as part of a study protocol. Methods: A Liver Psychology Clinic was created to run simultaneously with the Liver Treatment Clinic and a support group was initiated for patients on therapy. Results: Patient #1 is a 47-year-old African-American Vietnam veteran with chronic hepatitis C, genotype 1B, Stage III, who suffers from severe, chronic Post Traumatic Stress Disorder(PTSD) with suicidal ideation and history of prolonged hospitalizations, on trazodone, paroxetine hydrochloride (Paxil) and zolpidem tartrate (Ambien). He also has an extensive history of intravenous drug use. With supportive therapy and psychiatric consultations at regular intervals, during which suicidality and drug cravings were the primary focus, patient was able to manage side effects of treatment as well as negotiate through triggering events that often would have instigated heightened PTSD symptoms. Patient #2 is a 45-year-old African-American non-combat veteran with Chronic hepatitis C, genotype 1a, Stage III disease with a long history of intravenous drug use and intensive inpatient and outpatient drug treatment. On the 15th to 17th week of Rebetron treatment, patient had a major depressive episode with suicidal thoughts. He was prescribed Sertraline and began individual therapy sessions with the team psychologist with successful completion of therapy. Both patients completed treatment without having to reduce medication dose and able to function well both at work and home environment for the duration of treatment. Psychologists presence increased physician confidence and enabled the team to maintain treatment without dose reductions and discontinuations. Conclusions: In patients with major psychiatric illnesses combination therapy can be offered safely in a team environment with the inclusion of a psychologist.
Abstracts
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392 Alpha-1 antitrypsin genotypes in cirrhotic livers with PAS-D(ⴙ) globules: coexistense with other liver disease and outcome after liver transplant (OLTx) Asif Khalid1, Sydney Finkelstein2, Jawad Ahmad1, Mohammad Imtiaz1, Obaid A Shakil1, Patricia A Swalsky2, Forrest S Dodson3, John J Fung3, Jorge Rakela3, Anthony J Demetris3 and Hugo E Vargas2. 1Pathology, University of Pittsburgh, Pittsburgh, Pa; and 2Thomas E Starzl transplant institute, University of Pittsburgh, Pittsburgh, Pa. Purpose: Histological features of A1AT deficiency (A1ATD) in the liver include the presence of PAS-D(⫹) globules. This finding however has been reported in other liver diseases as well. The use of serum electrophoresis and tissue genotyping in detecting these proteins has revealed discrepancies raising the possibility of erroneous diagnosis. Furthermore patients with A1ATD often have other etiologies for their liver disease. The long-term outcome after OLTx for A1ATD related cirrhosis and the impact of co-existing liver diseases remains unclear. AIMS: (1) To determine the A1AT genotypes in patients with PAS-D(⫹) globules and cirrhosis and (2) To assess the impact of co-existing liver diseases on patient outcome after OLTx for A1ATD related cirrhosis. Methods: Clinical data and liver explant tissue on patients with PAS-d(⫹) globules transplanted between 1989-95 at the University of Pittsburgh was collected. Tissue based PCR/ Genotyping was performed. Data post OLTx to 06/00 was obtained Results: Native liver tissue was available in 70 cases (50 males) that had undergone 78 OLTx. Mean age at OLTx was 52Y and median follow-up 7.5Y (range ⬍1-11.2Y). During this period 23 deaths occurred. Median graft survival was 7.3Y. A1ATD was the primary diagnosis in 14 cases and common coexisting diagnoses were alcoholic-23, HCV-8, autoimmune-4 and cryptogenic cirrhosis-13. Genotypes (MZ-52, ZZ-9, ZS-5, SS-1 and 3 normal/MM) did not match available pre OLTx Pi types by electrophoresis in more than half cases (18 of 32)(Spearman’s rho ⫽ 0.43). A1AT levels for ZZ genotype was significantly lower (p ⬍ 0.05) than other genotypes. There was no difference in overall outcome or graft survival after OLTx by diagnosis or A1AT genotype Conclusions: Adult cirrhotic with PAS-D(⫹) globules on liver histology usually have MZ genotype. Outcome after OLTx does not appear to be affected by co-existing liver diseases or genotype. Diagnosis of A1ATD based on the presence of PAS-D(⫹) globules on hepatocytes and serum electrophoresis is sub-optimal. We recommend Genotyping for the most accurate diagnosis.
393 Vibrio parahaemolyticus as a cause for necrotizing fasciitis in a patient with cirrhosis Houssam Al Kharrat, MD, Shams Tabrez, MD, Richard Link, MD and Ingram Roberts, MD, FACG*. 1Gastroenterology, Yale Health System, Bridgeport Hospital, Bridgeport, CT, United States. Purpose: Vibrio parahaemolyticus infection is responsible for a selflimiting gastroenteritis in the majority of patients but may present as necrotizing faciitis. Methods: Patients with hepatic disease are most vulnerable to invasive infection, probably because of poor phagocytic function of neutrophils and functional bypass of the hepatic reticuloendothelial system as a result of portal hypertension. We are presenting a 59 year old male with a past medical history significant for alcoholic cirrhosis and portal hypertension. The patient had consumed oysters two days before. He was admitted complaining of (leg swelling), he had been started one antibiotics as an out patient. The swelling progressed and he began to show signs of necrotizing fasciitis, and bacteremia. (progress pictures of the patient included). The patient required a prolonged hospitalization with surgical debridement and eventual skin grafting. Vibrio parahaemolyticus was isolated from the wound culture and the blood.
Abstracts
Also the mean PyNPase level in the metastatic tumor foci was significantly higher than that in normal surrounding tissues (p ⫽ 0.009). Conclusions: PyNPase levels in both primary tumor and metastasized hepatic tumor foci were significantly higher than those in normal surrounding tissues. Therefore, it was suggested that determination of PyNPase levels in various tissue specimens obtained from patients with progressive large bowel cancer metastasized to the liver may aid in predicting the therapeutic effects of treatment with 5⬘-DFUR.
388 Danazol associated hepatic lesions Alaa G. Iskandar, MD, Sandy Gulati, MD, and Abhijit Kulkarni, MD*. 1 Gastroenterology, Allegheny General Hospital, Pittsburgh, PA, United States. Purpose: Anabolic androgenic steroids are commonly used in the treatment of various autoimmune conditions including idiopathic thrombocytopenic purpura (ITP). Case reports have associated danazol with benign as well as malignant hepatic lesions. Danazol is a pituitary gonadotropin antagonist with weak androgenic effects. We report the occurrence of a hepatic lesion consistent with hepatic adenoma in one patient receiving long-term danazol therapy for ITP. Methods: A 76 year old white male with a ten year history of steroid refractory ITP was subsequently placed on Danazol. After five years of therapy, a CT scan was obtained to evaluate nephrolithiasis, during which time an incidental 6 cm lesion was seen in the right hepatic lobe. A biopsy of this lesion was precluded due to its peridiaphragmatic location. A year later, the patient presented to the ER with a 48 hour history of sharp intermittent RUQ pain. Physical examination was significant for tender hepatomegaly. CT scan revealed an increase in the size of the previously found hepatic lesion to 12 cm and was associated with hemorrhage. In lieu of the above findings, the patient underwent a mesenteric angiogram which revealed bleeding arising from the right inferior and left hepatic arteries. A mass like lesion was seen fed by both vessels. Gelfoam embolization was successfully performed. Three months later, a follow up MRI of liver with gadolinium showed a reduction in size of the hepatic lesion. AFP and CEA were persistently normal. Results: The differential diagnosis of this lesion includes hepatic adenoma, hemangioma, focal nodular hyperplasia, hepatocellular carcinoma and metastatic disease. The combination of clinical history and radiographic findings in this patient suggested a hepatic adenoma, particularly in view of long term Danazol use. This patient’s hepatic lesion is consistent with the typical features seen in adenoma: rapid growth, large size and intratumor hemorrhage. The sudden onset of RUQ pain by our patient was most likely due to the extensive hemorrhage into the tumor. Hepatocellular adenomas are benign lesions with a prevalence of 3/100,000. They have been observed in women taking oral contraceptives and are associated with the use of anabolic steroids. They occur mainly in the right lobe of the liver. Treatment of hepatic adenomas should include cessation of steroids since it causes shrinkage or resolution of the hepatic tumors. Surgery is reserved for symptomatic patients. Conclusions: Benign hepatic lesions may be seen in patients on long term anabolic steroid therapy. Serial ultrasonography should be performed in these patients.
389 Our experience with percutaneous liver biopsy performed under IV propofol sedation Thirumalesh P Kanchana1, Shivakumar Vignesh1, Vivek Kaul1, Surakit Pungpapong2, Kenneth D Rothstein3 and Santiago J Munoz3*. 1 Gastroenterology; 2Medicine; and 3Hepatology, Albert Einstein Medical Center, Philadelphia, PA, United States. Purpose: Percutaneous liver biopsy (LB) for the diagnosis of liver disease is a well-established and routinely used procedure. Because of the necessity
AJG – Vol. 96, No. 9, Suppl., 2001
for the patient to cooperate with breath holding during the procedure, LB is performed by most physicians without any pre-procedure sedation. However, it is invasive and often patients have significant pain and anxiety. Propofol (PFL) is an anesthetic agent, which has been used for induction and maintenance of anesthesia as well as for sedation. PFL by continuous infusion provides a readily titratable level of sedation and a rapid recovery once infusion is terminated. In comparison with midazolam when used to maintain sedation, PFL provides equal or better control and more rapid recovery. Even though there are some published data regarding the midazolam sedation for LB, there is no data published in the literature to-date regarding the use of IV PFL for LB. Methods: Data from all the patients who underwent LB in our institution by one of the authors during two years from 10/98 to 10/00 were reviewed. All LB done under IV PFL sedation during this period were analyzed. Out of 81 patients who had undergone LBs during this period, 49 patients had had IV PFL sedation based on their preference. All the patients received PFL by anesthesiologist and were observed till complete recovery. Results: Patients were between 19 to 55 years of age (mean 43.8). 36 patients were males (73.5%) and 13 (26.5%) were females. 44 patients had Hepatitis C (89.8%), 3 had chronic hepatitis, 1 autoimmune hepatitis, and another patient had NASH. Two patients with Hepatitis C also were positive for HIV infection and 1 patient with Hepatitis C also had coinfection with Hepatitis B. All the patients recovered from the sedation rapidly and were discharged the same day of LB. However, one patient was readmitted the next day with pain. The average size of the specimen was14.1 mm (range 4 –30 mm) and the pathologists were able to make an accurate diagnosis in all cases. Conclusions: PFL sedation can be used successfully in patients undergoing liver LB. Patients can be sedated completely and LB can be obtained with no anxiety or pain. All the patients tolerated the procedure well. LB was done successfully in all the patients with adequate tissue samples. Although none of the patients in this study had major complications, a much larger study using PFL for LB is needed to assess the complication rate. IV PFL sedation can be especially helpful in highly anxious or uncooperative patients and who may need multiple LBs due to their chronic liver disease.
390 The proto-oncogene Akt is expressed in hepatocellular carcinoma: potential target for chemoprevention by sulindac William J Karolski1, Rodney M Markin2, Timothy M McCashland1 and Hemant K Roy1*. 1Internal Medicine, University of Nebraksa Medical Center, Omaha, Nebraska, United States; and 2Pathology, University of Nebraska Medical Center, Omaha, Nebraska, United States. Purpose: The mortality from hepatocellular carcinoma (HCC) in this country is rapidly rising, underscoring the need for chemoprevention. Nonsteroidal antiinflammatory drugs (NSAIDS) have been demonstrated to prevent GI malignancies through both cyclooxygenase (COX)2-dependent and -independent mechanisms. COX 2 has been demonstrated to be overexpressed in HCC, but only in the subset of well-differentiated tumors. The proto-oncogene Akt has recently been demonstrated to be a NSAID target. This serine-threonine kinase has a myriad of potentially neoplastic actions including increasing cellular proliferation, inhibiting apoptosis and stimulating angiogenesis. Therefore, we wanted to evaluate Akt expression in HCC and determine if NSAIDs would modulate expression and/or activity in human HCC cell lines. Methods: Immunohistochemistry was performed on 26 HCC with a polyclonal antibody to Akt 1/2. Slides were developed with a Vectastain ABC kit. Two human HCC cell lines (HepG2 and HuH7) that have different molecular genetic characteristics were treated for 5 days with either sulindac 800 M or vehicle. Cell counts were obtained. Following, cell lysates were made and subjected to immunoblot analysis using a polyclonal antibody to Akt 1/2, serine-473 phosphorylated Akt (the activated form) or PARP (a marker of apoptosis). Xerograms were developed with enhanced chemiluminescence and quantitated by laser densitometry.
AJG – September, Suppl., 2001
Results: Akt was detectable in all human HCC. Importantly, Akt was also seen in the surrounding hepatocytes, implying that Akt expression occurs early during carcinogenesis. In cell culture, sulindac treatment resulted in an approximate decrease in cell number by one-half, with a concomitant increase in PARP degradation, suggesting an induction of apoptosis. In HepG2 and HuH7 cell lysates, Akt expression decreased to 75.7 ⫾ 2.9% and 75.8 ⫾ 3.3% of vehicle, respectively (both p ⬍ 0.001). Moreover, the activated Akt form was decreased to 79 ⫾ 5% and 59 ⫾ 4% (p ⬍ 0.001) of vehicle in the Hepg2 and HuH7 cell lines, respectively. Conclusions: We confirm that sulindac may be effective against HCC by inducing apoptosis. Furthermore, our data indicates that Akt is a potential target in that it is expressed in HCC and is both downregulated and inactivated by sulindac. This data provides further support for the use of NSAIDS as a chemopreventive agent against HCC.
391 Impact of psychology evaluation clinic on Rebetron therapy in highrisk mental health patients Gayle Kelsey, Psy.D.1, Daniel Feld, M.A.1, Marna T. Abarientos1 and Ayse Aytaman, M.D.1*. 1Gastroenterology, VA NY Harbor HCS Brooklyn Campus, Brooklyn, New York, United States. Purpose: Patients with chronic hepatitis C infection who have a major affective disorder, as classified by the Diagnostic and Statistical Manual– Fourth Edition (DSM-IV), and a significant history of suicidal or homicidal ideation are not treated with combination therapy (interferon alpha 2B/ ribavirin) because of the risk of severe psychiatric side effects that often arise with treatment. Most United States veterans infected with hepatitis C virus (HCV) are Vietnam-era veterans with significant psychiatric comorbidities that would normally exclude them from therapy. This report will illustrate the successful completion of treatment with Rebetron in two veterans with significant psychiatric comorbidities as part of a study protocol. Methods: A Liver Psychology Clinic was created to run simultaneously with the Liver Treatment Clinic and a support group was initiated for patients on therapy. Results: Patient #1 is a 47-year-old African-American Vietnam veteran with chronic hepatitis C, genotype 1B, Stage III, who suffers from severe, chronic Post Traumatic Stress Disorder(PTSD) with suicidal ideation and history of prolonged hospitalizations, on trazodone, paroxetine hydrochloride (Paxil) and zolpidem tartrate (Ambien). He also has an extensive history of intravenous drug use. With supportive therapy and psychiatric consultations at regular intervals, during which suicidality and drug cravings were the primary focus, patient was able to manage side effects of treatment as well as negotiate through triggering events that often would have instigated heightened PTSD symptoms. Patient #2 is a 45-year-old African-American non-combat veteran with Chronic hepatitis C, genotype 1a, Stage III disease with a long history of intravenous drug use and intensive inpatient and outpatient drug treatment. On the 15th to 17th week of Rebetron treatment, patient had a major depressive episode with suicidal thoughts. He was prescribed Sertraline and began individual therapy sessions with the team psychologist with successful completion of therapy. Both patients completed treatment without having to reduce medication dose and able to function well both at work and home environment for the duration of treatment. Psychologists presence increased physician confidence and enabled the team to maintain treatment without dose reductions and discontinuations. Conclusions: In patients with major psychiatric illnesses combination therapy can be offered safely in a team environment with the inclusion of a psychologist.
Abstracts
S125
392 Alpha-1 antitrypsin genotypes in cirrhotic livers with PAS-D(ⴙ) globules: coexistense with other liver disease and outcome after liver transplant (OLTx) Asif Khalid1, Sydney Finkelstein2, Jawad Ahmad1, Mohammad Imtiaz1, Obaid A Shakil1, Patricia A Swalsky2, Forrest S Dodson3, John J Fung3, Jorge Rakela3, Anthony J Demetris3 and Hugo E Vargas2. 1Pathology, University of Pittsburgh, Pittsburgh, Pa; and 2Thomas E Starzl transplant institute, University of Pittsburgh, Pittsburgh, Pa. Purpose: Histological features of A1AT deficiency (A1ATD) in the liver include the presence of PAS-D(⫹) globules. This finding however has been reported in other liver diseases as well. The use of serum electrophoresis and tissue genotyping in detecting these proteins has revealed discrepancies raising the possibility of erroneous diagnosis. Furthermore patients with A1ATD often have other etiologies for their liver disease. The long-term outcome after OLTx for A1ATD related cirrhosis and the impact of co-existing liver diseases remains unclear. AIMS: (1) To determine the A1AT genotypes in patients with PAS-D(⫹) globules and cirrhosis and (2) To assess the impact of co-existing liver diseases on patient outcome after OLTx for A1ATD related cirrhosis. Methods: Clinical data and liver explant tissue on patients with PAS-d(⫹) globules transplanted between 1989-95 at the University of Pittsburgh was collected. Tissue based PCR/ Genotyping was performed. Data post OLTx to 06/00 was obtained Results: Native liver tissue was available in 70 cases (50 males) that had undergone 78 OLTx. Mean age at OLTx was 52Y and median follow-up 7.5Y (range ⬍1-11.2Y). During this period 23 deaths occurred. Median graft survival was 7.3Y. A1ATD was the primary diagnosis in 14 cases and common coexisting diagnoses were alcoholic-23, HCV-8, autoimmune-4 and cryptogenic cirrhosis-13. Genotypes (MZ-52, ZZ-9, ZS-5, SS-1 and 3 normal/MM) did not match available pre OLTx Pi types by electrophoresis in more than half cases (18 of 32)(Spearman’s rho ⫽ 0.43). A1AT levels for ZZ genotype was significantly lower (p ⬍ 0.05) than other genotypes. There was no difference in overall outcome or graft survival after OLTx by diagnosis or A1AT genotype Conclusions: Adult cirrhotic with PAS-D(⫹) globules on liver histology usually have MZ genotype. Outcome after OLTx does not appear to be affected by co-existing liver diseases or genotype. Diagnosis of A1ATD based on the presence of PAS-D(⫹) globules on hepatocytes and serum electrophoresis is sub-optimal. We recommend Genotyping for the most accurate diagnosis.
393 Vibrio parahaemolyticus as a cause for necrotizing fasciitis in a patient with cirrhosis Houssam Al Kharrat, MD, Shams Tabrez, MD, Richard Link, MD and Ingram Roberts, MD, FACG*. 1Gastroenterology, Yale Health System, Bridgeport Hospital, Bridgeport, CT, United States. Purpose: Vibrio parahaemolyticus infection is responsible for a selflimiting gastroenteritis in the majority of patients but may present as necrotizing faciitis. Methods: Patients with hepatic disease are most vulnerable to invasive infection, probably because of poor phagocytic function of neutrophils and functional bypass of the hepatic reticuloendothelial system as a result of portal hypertension. We are presenting a 59 year old male with a past medical history significant for alcoholic cirrhosis and portal hypertension. The patient had consumed oysters two days before. He was admitted complaining of (leg swelling), he had been started one antibiotics as an out patient. The swelling progressed and he began to show signs of necrotizing fasciitis, and bacteremia. (progress pictures of the patient included). The patient required a prolonged hospitalization with surgical debridement and eventual skin grafting. Vibrio parahaemolyticus was isolated from the wound culture and the blood.