Autoimmune overlap syndrome: is there a specific treatment?

Autoimmune overlap syndrome: is there a specific treatment?

S100 Abstracts AJG – Vol. 97, No. 9, Suppl., 2002 estimate the incidence of variceal bleeding in patients with cirrhosis due to chronic HCV who are...

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S100

Abstracts

AJG – Vol. 97, No. 9, Suppl., 2002

estimate the incidence of variceal bleeding in patients with cirrhosis due to chronic HCV who are awaiting liver transplantation. Methods: 177 pre–transplant patients were the subject of this analysis. All patients had upper endoscopy for evaluation of esophageal and/or gastric varices as well as presence and grade of portal hypertensive gastropathy. Patients were classified into four groups according to etiology of cirrhosis: ETOH 31, HCV 63 HCV/ETOH 46, and others 37. Results: 80.7% (25) of ETOH patients had esophageal varices versus 63.5% (40) of HCV patients, 67.4% (31) of HCV/ETOH, and 75.7% (28) in liver cirrhosis due to other etiologies. There is no difference between the groups with respect to grade of varices. Portal hypertensive gastropathy by different grades was detected in 74.1% , 54%, 67.4%, and 64.9% of the 4 groups respectively. There was no statistical difference in portal hypertensive gastropathy grades between the groups. The ETOH group had significantly higher incidence of bleeding especially compared to the HCV group (p⫽0.0004). Despite having similar prevalence of varices, variceal bleeding was less in patients with HCV than the other groups(table). Variceal Bleeding ETOH

HCV

N 31 63 Incidence of Variceal Bleeding 61.3% (19) 23.8% (15)

ETOH/HCV

OTHER

46 30.4% (14)

37 32.4% (12)

Conclusions: 1) Cirrhosis due to chronic HCV infection had less variceal bleeding than other causes of cirrhosis. 2) Patients with cirrhosis due to ETOH have higher incidence of bleeding than patients with cirrhosis due to other etiology. 304 FUSOBACTERIUM – AN UNDERECOGNIZED ETIOLOGY OF PYOGENIC LIVER ABSCESS: CASE REPORT Nirmala Shanmugam, M.D. and Enrique G. Molina, M.D.*. Department of Gastroenterology and Hepatology, University of Miami School of Medicine, Miami, FL. Purpose: Fusobacterium bacteremia is a rare cause of liver abscess in humans. It is a commensal found in the oral cavity, gastrointestinal tract and urogenital tracts. We report an unusual case of multiple hepatic abscesses caused by Fusobacterium necrophorum in a young immunocompetent male. A previously healthy 25 year old male from Guatemala, was referred to our hospital for further evaluation of fever, headache, and leucocytosis. He was well until a week prior to admission. Chief complaints included vague abdominal discomfort, fever, and chills. Broad spectrum antibiotics were administered at the previous hospital with no resolution of fever. Past medical history was significant for a bicuspid aortic valve. On physical examination, he was febrile (101F), and was found to be icteric. No obvious dental disease was identified. Abdominal examination did not reveal hepatosplenomegaly. Laboratory data revealed leucocytosis, and elevation of alkaline phosphatase. Hepatic transaminases were in the normal range. Initial work up of fever included blood culture. Echocardiogram done did not reveal any cardiac vegetation. CT scan of the abdomen done revealed multiple hypodense lesions in the liver consistent with hepatic abscesses. Antibiotic therapy with Imipenem and Metronidazole was initiated. One of the abscesses was aspirated under ultrasound guidance. 20 cc of brownish fluid was aspirated, and gram stain revealed gram negative rods. Cultures from the blood as well as the aspirated material grew Fusobacterium necrophorum. Patient responded well to therapy with complete resolution of fever and normalization of white count. Patient was discharged home and continued on oral Metronidazole therapy for 6 weeks. Conclusion: Fusobacterium is an anaerobic gram negative rod, belonging to family Bacteroidaceae. It is a common cause of liver abscess in cattle. F.necrophorum has been reported to cause severe bacteremic illness in humans. It very rarely produces hepatic abscess in immunocompetent human host. The origin of the septicemia and hepatic abscess may be secondary to a dental cleaning which our patient underwent a few months

prior to presentation. A very high index of suspicion is necessary to make a timely diagnosis of this unusual disease and to initiate appropriate therapy, and avoid the high mortality associated with this disease. 305 EUS DIRECTED FNA AND/OR TRU–CUT BIOPSY IN HIGH RISK PATIENTS WITH ADVANCED LIVER DISEASE WITH LIVER MASS(ES): A VIABLE ALTERNATIVE Allan P. Weston, M.D.* and Daniela Mitreva, M.D. GI–Liver Section, VAMC, Kansas City, MO. Purpose: Liver lesions can be noted in cirrhotic patients either at initial screening or during surveillance HCC examinations. These liver lesions can be problematic from the standpoint of tissue diagnosis when they are noted in the setting of advanced cirrhosis complicated by ascites, coagulopathy and hypersplenism. We describe our centers experience with tissue acquisition utilizing endoscopic ultrasonographic directed fine needle aspiration (EUS–FNA) or tru– cut biopsy (EUS– bx) of suspected HCC masses in patients with advanced cirrhosis. Methods: Patients with cirrhosis and liver masses noted on CT since 12/01 underwent trans–abdominal probe US (Dornier) alone or in conjunction with EUS (Olympus UC–30P). Tissue samples were obtained either percutaneously by Color Doppler directed ultrasonography using a 16 gauge aspiration needle or via EUS using Olympus NA–10J–1 needle or Wilson– Cook Biopsy needle. Post procedure, patients were observed for 1 to 4 hours, and then discharged from endoscopy recovery room unit. Complications from the procedure were assessed by scheduled phone interviews and follow up clinic visits. Results: 114 patients underwent US examinations over the 6 month period, 10 of whom were for evaluation of a liver mass(es) in setting of advanced cirrhosis. Probe US showed liver mass in central liver region in 2, right lobe in 4 and left lobe in 3. In one patient, the liver lesion seen on CT was isoechoic on US. 6/10 patients had significant coagulopathy alone, 4/10 significant coagulo–pathy and thrombocytopenia. In addition, 3 patients had concurrent ascites. Probe directed aspiration biopsy was done in 2 patients, both with large massess involving right lobe of liver, both which were diagnostic of HCC. In both cases pre–procedure FFP and/or DDAVP was given. The remaining 7 patients underwent EUS–FNA/ bx that was definitive in 5 (HCC –3, non–small cell cancer – 1, adenocarcinoma – 1), highly suspcious for cancer in 1 and non– diagnostic in one (in whom procedure was terminated prematurely after due to patient uncooperativeness). No complications (bleeding, infection, perforation, death , etc) were encountered. Conclusions: EUS–FNA and EUS– bx can be safely performed in high– risk, advanced cirrhotic patients in order to obtain histologic diagnosis to direct further therapy. 306 AUTOIMMUNE OVERLAP SYNDROME: IS THERE A SPECIFIC TREATMENT? Octavio Gomez–Escudero, M.D., Alfonso Zetina–Lopez, M.D. and Marco A. Olivera–Martinez, M.D.*. Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, D.F., Mexico. Purpose: Patients with clinical, biochemical, immunological and histological features of two autoimmune liver diseases (ALD) (i.e., autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC)) are known to have an autoimmune overlap syndrome (AIOS). Although no specific therapy has been found, previous studies have reported contradictory findings using steroids, and even there are reports of spontaneous biochemical improvement without treatment. Specific Aim: To evaluate biochemical response of patients with AIOS to three different combination of agents known to improve single ALDs. Methods: Patients meeting diagnosis of AIOS included those with well– established criteria of an ALD (either PBC or AIH) plus 3 out of 4 criteria of another. We then reviewed retrospectively biochemical response to three

AJG – September, Suppl., 2002

different combination of medications. Twenty– eight patients met our criteria, and two of those did not receive specific treatment. Of the 26 left, 12 (46%) received either prednisone (PDN) or azathioprine (AZT) at standard doses for AIH treatment; 8 (30%) received ursodeoxycholic acid (UDCA) plus colchicine at standard doses for PBC (according to institutional protocols), and 6 (24%) received the combination of either PDN or AZT plus UDCA and colchicine.

Abstracts

S101

In a multivariate analysis, tumor volume more than 50% of total liver mass measured by imaging studies, p 0.001 (CI 1.64 –7.70 95%), and having 3 or more tumors, p 0.023 (CI 1.05–2.02 95%) were independent predictors of survival. Neither Child–Pugh nor Okuda classifications had any influence on median survival time. Patients survived significantly longer, when treated with liver resection. Median survival for all patients with HCC was 7.95 months. Conclusions: Our patients with HCC had a poor median survival. HCC not only occurred in patients with liver cirrhosis in a proportion similar to that reported elsewhere. Comparing the most important prognostic parameters, we found that the course and survival time of HCC can be predicted by two easily measurable variables: tumor volume more than 50% of total liver mass, and having 3 or more tumors. 308

Results: Among patients receiving PDN or AZT alone, 8 out of 12 (66%) developed sustained biochemical response. Of patients receiving UDCA plus colchicine, 5 out of 8 (62%) improved biochemically, and of those receiving the combination of PDN or AZT plus UDCA/Colchicine, 5 out of 6 (83%) improved initially, however, only 3 (50%) had sustained response. Neither the presence of specific auto–antibodies, nor histological findings affected biochemical response. Conclusions: In this study, patients with AIOS receiving combination therapy with PDN or AZT plus UDCA/Colchicine showed an early biochemical response better than those receiving either treatment alone, however, sustained response was no different than that achieved with either drug. Patients with higher AIH scores were more likely to respond to UDCA/Colchicine and combination therapy, however, no correlation was found between response and the presence of auto–antibodies or predominant histology for a specific ALD. Larger and prospective studies are required to define the role of each of these therapies for patients with AIOS. 307 HEPATOCELLULAR CARCINOMA (HCC) IN A MEXICAN COHORT: PROGNOSTIC FACTORS AFFECTING SURVIVAL Aldo J. Montano, M.D., Judith Meza, M.D., Marco A. Olivera, M.D.* and Myrna Candelaria. Gastroenterology and Oncology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, DF, Mexico. Purpose: HCC ranks fifth among all cancers worldwide. For most patients HCC is a terminal complication of a chronic inflammatory and fibrotic liver disease. Only a few follow– up data are available for patients with HCC in Latin–America. Therefore we analyzed all HCC admitted to The Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran, a national referral center between 1991 and 2000. All patients were third generation Mexicans. Methods: All 135 patients seen at the INCMNSZ, from 1991 to 2000 were included in this retrospective study. We documented etiology, stage (Okuda and TNM), presence of liver cirrhosis and Child–Pugh score, diagnostic and therapeutic approaches. Factors determining survival time were analyzed by univariate and multivariate analysis using Cox proportional hazard regression models. Survival time was calculated as a function of staging and therapy. Results: One hundred and thirty–five consecutive patients were included: 77 (57%) were males. Mean age at HCC diagnosis was 59.2 years (16 – 87). Cirrhosis was diagnosed in 89 patients (64.4%). Seventy– eight (58%) were positive for HCV antibodies, 14 (10%) had HBsAg, and 24 (18%) had alcoholic cirrhosis. Twenty–two patients (16.3%) underwent liver resection, 10 (7.4%) transarterial chemoembolization, 6 (4.4%) percutaneous ethanol injection, 5 (3.7%) systemic chemotherapy, 11 (8.1%) tamoxifen and 1 (0.7%) thalidomide. Eighty patients (59.3%) received no treatment.

TREATMENT RESPONSE RATES OF U.S. VETERANS IN BROOKLYN WITH CHRONIC HEPATITIS C INFECTION Ayse Aytaman, M.D.*, Marna T. Abarientos, JoAnn Comas, R.N., Anna Christakos–DiTeodoro, Pharm.D., Gerald Fruchter, M.D. and Gail Kelsey, Psy.D. Gastroenterology, VA New York Harbor HCS, Brooklyn Campus, Brooklyn, NY. Purpose: Data from 116 patients treated in the Brooklyn campus were collected. Twenty–four patients discontinued therapy for various reasons with a 3.4% drop out rate for non– compliance/active drug use and 17.2 % of patients unable to tolerate the side effects of treatment. We are presenting treatment response data with analysis of the factors affecting poor treatment response. Methods: Data was collected from 116 patients initiated into therapy under various IRB approved treatment protocols which included patient demographics, medical history (co–morbidities), mental health history, HCV status at baseline, at the end of therapy and at post–treatment follow– up. All treatment protocols involved the use of either interferon monotherapy (8), Rebetron combination therapy (98), PEG–Intron monotherapy (1) or PEG–Intron ⫹ ribavirin combination therapy (9). HCV status was based on viral load testing by polymerase chain reaction (PCR) by Roche–Amplicor assay. Results: Ninety–two (92) completed the treatment regimen. Sixty (65.2%) patients were nonresponders to therapy with detectable viral RNA by PCR at six months of therapy. Thirty–two (34.8%) patients had negative HCV RNA at the end of therapy. Sustained treatment response data are available on 84 patients. Fourteen (16.6%) patients have sustained virologic response at 6 months post treatment follow– up with ten (11.9%) relapsers. Strict intent to treat analysis of data is pending completion of the 6 –month post treatment follow– up in 8 patients. Looking into the various factors affecting the treatment response of our patient population, 81.0% of patients have non 2 and 3 HCV genotype, 30.2% are African American, 19% are Hispanic, with 42.3% of patients diagnosed with stage III to IV liver disease on biopsy, 56% with a history of significant alcohol use and 61.2% were considered obese with a body mass index (BMI) of greater than 27%. Conclusions: U.S. veterans in Brooklyn have poor response rates to currently available HCV treatments. These are closely correlated with a higher rate of genotype 1 patients, more advanced liver disease, significant history of alcohol abuse, high BMI rates, and a population demographic with a higher incidence of African Americans. 309 NON–INVASIVE MEASUREMENT OF THE ESOPHAGEAL VARICES PRESSURE USING BALLOON METHOD: CORRELATION WITH FINE NEEDLE PUNCTURE METHOD & ANALYSIS WITH CORRELATION FACTORS Ming–Chih Hou, M.D.*, Tsu–Te Liu, M.D., Han–CHieh Lin, M.D., Full–Young Chang, M.D. and Shou–Dong Lee, M.D. Division of Gastroenterology, Department of Medicine, Veterans General Hospital– Taipei, Taipei, Taiwan and Faculty of Medicine, National Yang–Ming University, Taipei, Taiwan.