HEPATOLOGY Vol. 34, NO. 4, Pt. 2, 2001 AASLD ABSTRACTS 6 6 3 A

1963

LIVER TRANSPLANT CANDIDATES WITH HEPATOCELLULAR CARCI- NOMA: A RETROSPECTIVE ANALYSIS OF THEIR EVALUATION AND OUTCOME. Noriyo Yamashiki, Tomoaki Kato, K. Rajender Reddy, Abhasnee Sobhonslidsuk, Seigo Nishida, David Levi, Eugene R Sehiff, Andreas G Tzakis, Division of Hepatology and Liver Transplantation, University of Miami School of Medicine, Miami, FL

Background: Orthotopic liver transplantation (OLT) is an effective therapeutic mo- dality for patients with cirrhosis and hepatocdlular carcinoma (HCC). The increas- ing incidence of HCC in the United States and the acceptance of OLT as a therapy for carefully selected candidates has led to an increase in the number of such patients presenting for OLT evaluation, However, the outcome of this population is not clear. Aims: To determine the number of patients with HCC referred to a large transplant center and subsequently the frequency of their listing for OLT. We also set out to analyze the transplant rate after listing, survival rate, and the frequency and reason for de-listingwhile awaiting liver transplantation. Methods: Between 1997 and 2000, 2,356 patients were referred for liver transplant evaluation to University of Miami liver transplant program. Of those, 118 (5.0%) were referred either with a diagnosis of HCC or had HCC that was newly discovered during their evaluation. There were 79 men and 39 women; mean age was 55 years (range 11-77). All had cirrhosis. Data including patient demographics, UNOS status, tumor stage and histology, and AFP levels, were collected retrospectively. Mode of tumor detection and the reason for de-listing were also recorded. Results: Ninety-one of 118 patients (77%) were listed for liver transplantation, whereas remaining 27 patients were not considered to be OLT candidates due to resectable tumor (1), advanced minor stage (13) and other reasons (13). Of the 91 candidates, 60 (66 %) were transplanted with median waiting time of 102 days (1-1166) [OLT group], however 18 patients (20%) were removed from the list in median period of 145 (1-185) days [De-listed group]. Four patients are currently active on UNOS waiting list as status 2B or 3, and 1 died while listed. Remaining 8 patients have been listed due to the severe liver disease, but our eval- uation has not revealed any evidence of HCC. The OLT group and the de-listed group were similar with regard to patient demographics. They were statistically different, however, with regard to AFP level and the number of lesions (single/ multiple). Survival at I and 2 year after referral was 91% and 73% in OLT group, and 73 % and 49 % in de-listed group, although this trend was not statistically different. In the OLT group, HCC was histologically proven in 57 of the explants, whereas HCC was not found in 3 cases who had an elevated AFP but with equivocal radio- graphic findings. Reasons for de-listing were tumor progression (14), logistical rea- sons (2) and non-compliance (2). Tumor progressed in 8/14 patients in spite of adjuvant therapy; PEI (1), TACE (5), and MCT (2). Conclusion: At our center, 77 % of referral patients with HCC and cirrhosis were listed as liver transplant candidates initially and 20 % of listed candidates were de-listed mainly due to tumor progres- sion. Ahhough our data may represent a referral bias, it is encouraging that most patients with HCC referred to our transplant center were able to accomplish it and also able to remain listed.

1964

IMPLANTED DRUG DELIVERY SYSTEM FOR ADVANCED HEPATOCEL- LULAR CARCINOMA USING EPIRUBICIN LIPIDOL EMULSION. Sayed A Mahrakawy, Saleh A Ahmed, Maha M E1 Zimaity, Mohamed M Nageeb, Hazem M Abd E1 Salam, ainshams Univ, Cairo Egypt

A retrospective study was performed on 27 patients presented with advanced hepatocellular carcinoma (HCC) at the surgical department in AinShams Uni- versity hospitals, from Dec.1998 to Apr.2000.The aim of the study was to assess the efficacy of locoregional therapy by hepatic artery infusion (HAl) for advanced HCC.Fifteen patients received HA1 therapy with epirubicin lipidol emulsion using an implanted drug delivery system, whereas the remaining 12 patients refused treatment and were considered as control group.In the treated group,11 patients had a positive response,whereas 4 patients had a negative response;10 of them survived up to 6 months,whereas the remaining 5 patients survived up to 12 months.Those patients who survived up to 12 months were responders to our treatment.The mean duration of hospital stay after hepatic artery cannulation was 9(5-16) days.Nine patients received the treatment as outpatient.No patient in the control group survived up to 12 months.A cath- eter related trouble occurred in 3 patients,2 of them had mild cellulites around the port of the catheter which was easily controlled by antibiotics and the third patient had bleeding due to dislodged catheter which needed urgent surgery to control bleeding and to re-fix the catheter.In conclusion,HAI therapy is an effective method for treating unresectable HCC ,both for palliation of symp- toms as well as prolongation of survival with good quality of life.

1965

DETECTION OF 8-HYDROXY DEOXYGUANOSINE, INDUCIBLE NITRIC OXIDE SYNTItASE- AND OGG1-MRNAS DURING OCCURRENCE OF GLUTATHIONE-S-TRANSFERASE PLACENTAL FORM-POSITIVE FOCI. Shuichi Seki, Shuji Iwai, Hiroki Sakaguchi, Takuya Kitada, Norifumi Kawada, Shoji Fukushima, Osaka City University Medical School, Osaka Japan

Since glutathione-S-transferase placental form (GST-P)-positive loci are known as preneoplastic lesions of hepatocellular carcinoma (HCC) in rats, we detected DNA damage and repair of hepatocyte nuclei in addition to the caus- ative agent of DNA damage during this process. We induced GST-P positive loci in rats by administration of 2-amino-3,8-dimethylimidazole quinoxaline (MelQx) and carbon tetrachloride (CCL4), and immunohistochemically de- tected GST-P positive loci. We measured 8-hydroxy-deoxyguanosine (8- OHdG) as oxidative DNA damage by high-performance liquid chromatogra- phy with electrochemical detection by an adaptation of the method of Kasai et al, arid mRNA of inducible nitric oxide synthase (iNOS) as a causative agent of DNA damage and mRNA of OGG1 as a repair enzyme of DNA damage by RT-PCR using appropriate primers. The number of GST-P loci remarkably increased by administration of both MeIQx and CCL4 in comparison with the number of GST-P loci induced by MeIQx alone at 22 weeks (p < 0.05). The amounts of 8-OHdG and mRNA of OGG1 increased in the livers treated by both MelQx and CCL4 in comparison with those treated by MeIQx alone even at I week and thereafter following the administration (p < 0.01). The amounts of 8-OHdG formation and OGG-1 correlated to the number of GST-P loci. Expression of mRNA of iNOS increased in dose response manner of CCL4 with or without MelQx. In conclusion, the oxidative DNA damage and its repair mechanism may participate in carcinogenesis of HCC in rats. Therefore, we have to measure 8-OHdG, OGG1 and iNOS in the dysplastic nodules in human cirrhotic livers.

1966

SENSITIVITY AND SPECIFICITY OF ALPHA-FETOPROTEIN (AFP) IN U.S. PATIENTS WITH HEPATITIS C VIRUS-RELATED HEPATOCELLU- LAR CARCINOMA (HCV/HCC). Mindie H Nguyen, Stanford University, San Bruno, CA; Emmet B Keeffe, Stanford University, Palo Alto, CA; Teresa L Wright, University of California, San Francisco, San Francisco, CA

BACKGROUND: AFP has long been used as a diagnostic marker for HCC. Most dsta, however, have come from studies of atients with chronic hepatitis B or other liver diseases of mixed etolol gies. Limited and conflicting studies of the va~ue of AFP in the diagnosis of HCV/HCC have been conducted only in Asian axed European patients. METHODS: This is a retrospective case control study of the value of AFP in U.S. patients with HCV/I:ICC. Consecutive cases of HCV/HCC from 1998 to 2000 at the Veterans Administration Medical Center, San Francisco (VASB) and Stanford Hospital and Clinics (SHC) were studied, Cases from cytology andpathology records from 1995 to 1998 at VASF were also included. HCC was diagnosed by cytology (from fine*needla aspiration), histology (from resected surgical specimens, liver explants, andautopsies), or the presence of characteristic hepatic Glass on imaging studies (US. CT, and/or MRI). Controls include patients with HCV-related cirrhosis (H CV/C) without radiographic or clinical evidence of HCC obtained from the liver transplant list at SHC and liver biopsy records at VASF durir~g similar time periods. Non-parametric S,~earman rank and Ma nn-Whimey/Kruskal-Wallis correlations were computed for continuous and categorical variables, respectively. RESULTS: 82 HCV/HCC cases (33 at VASF, 49 at SHC) and 67 HCV/C controls (26 at VASF. 41 at SHC) were studied. 50 of the 82 cases were proven by cytology and/or histology. Among the HCV/HCC cases, mean age was 61, 90% were male, 54% were Caucasian, 9% were African American, 27°,4 were Asian, and 10% were other ethnic groups. Median tumor size at presentation was 3.6 cm (mean= 4.3 cm). median tumor mlmber was 1,0 (mean= 2.0), median number of hepatic lobar involvement was 1 .fl (mean = 1.4). and 21% had vascular invasion. Median Child/Turcotte-Pugh (CTP) and Model for End/Stage Liver Disease (MELD) scores were 7.0 and 9.0 respec- tively, with sm~ilar mean values. 40% of HCV/HCC cases were Child A and 32% ~a,ere Child B. When compared with controls, HCV/HCC cases were older and had higher alkaline phosphatase (ALP). alanine aminotransferase (ALT), aspartate aminotransferase (AST), and MELD (p<0.O01). Using cut-offs of 10, 15 and 20 for AFP. sensitivity was 79.3%, 69.5%, 62,2%, and specificity was 70.2, 83.6% and 86.6%. respectively An AFP cut-off value of 72 y~elded a specificity of 98,5% (95% CI =91.96%-99,96%) No significant correlation was found between AFP and patient ge~tder or age; tumor size, number, lobar involment, or vascular invasion; CTP or MELD or laharatol y tests including platelets, total bi irubin, ALP, ALT, or AST. African Americans with HCV/HCC had lower AFP than Caucasian and Asian ~ses (p=0,039) but the sample size was small. CONCLUSION: AFP is a useful diagnostic minor marker for HCC in HCV-infected U.S. patients. Sensitivity of AFP of 10.0 or hi her was 793%. Specificity of AFP of 72 or higher was 98.5%, virtually diagnostic of HCC, and might influence the ~agnostic approach to hapatic masses in patients with advanced chronic hepatitis C and cirrhosis.

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