H E P A T O L O G Y V o l . 22 , N o . 4, P t . 2, 1 9 9 5 A A S L D A B S T R A C T S 481A

1497 EVALUATION OF HEPATIC FIBROGENES1S 1N CHRONIC HEPATITIS C : CORRELATION OF KNODELL I. AND SERUM PROCOLLAGEN TYPE III B Rodrieues. C Machado. C Sousa. A Figueiredo. T Lopesl C Baptista. M Ramos. A Mouro. M Ouina - S.Univ.Medicina 11I ; S. Anat.Patol6gica- H.Pulido Valente, Lisbon, Portugal

AIM: to study the correlation between an available marker of hepatic fibrogenesis - serum procollagen type III ( PIIIP)- and the Histological Activity Index ( KnodelI I.) in chronic hepatitis C, their relation with epidemiological, biochemical and morphological data, and to follow the evolution of PIIIP values under Interferon ( IFN) therapy, as a predictor of initial response and late relapse. METHODS: We studied 32 patients ( 20 M ; 12 F - mean age: 42 years ) with chronic hepatitis C, diagnosed by persistent ALT elevation and positive serological tests (RIBAIUIII) and PCR for HCV-RNA. Assessment of liver biopsy was done by a single independent observer, applying the Knodell I. : c.persist.h.-8;c.lobul.h.-l; c.active h.-19; cirrhosis-4). Interferon therapy (3 MU,tiw, 12 months)was prescribed to 27 patients ; follow-up has been completed in 10 patients, with sequencial PIIIP dosage,after 6 and 12 months of IFN, using a RIA method - Farmos Diagnostica ( normal: 1,7-4,2 ug/1 ). RESULTS: The mean basal PIIIP value was 5,08~-3,64 ug/l, with a slight variation according to the histological severity of the disease ( c.pers.h- 3,36=1,13; c.active h-5,22.+,4,07 ; cirrhosis-7,85.+.3,28 ug/l )- NS tStud. Correlation with the Knodell I.( linear regression test) revealed a significant correlation between PIIIP and KI (r=0,574;p=0,00058) and between PIIIP and periportal (r=0,565;p=0,00074) and portal infiammmation scores ( r=0,496;p=0,003). The follow-up of treated cases demonstrated a suggestive but nonsignificant difference between responders ( 4,50+9,50 ug/1) and nonresponders (8,25,+.6,42 ug/1). Comparing the mean PIIIP values before and atler 6 and 12 months oflFN ( 6,01.+,3,1; 6,40_+.1,8 ; 3,82,1,0 ug/l ) we found a SS difference(tStud-p<0,00l) between the l~2th month value and the previous ones, occurring both in responders and nonresponders. Conclusions: The comparison of the Knodell I. with the PIIIP values allows an assessment of their significant correlation; mainly with the inflammation scores, that can provide an additionnal marker to follow IFN therapy in chronic hepatitis C, suggesting a trend for late improvement with a prolonged treatment course.

1498 SIGNIFICANCE OF ANTI-HCV-CORE lgM ANTIBODIES IN CHRONIC HEPATITIS C: COMPARISON WITH KNODELL INDEX (IK) AND RESPONSE TO INTERFERON B Rodrigues, I Ribeiro, A Coutinho, T Lopes, C Baptista, A Dias, M Ramos, J Pina, AM Mouro, M Quina. Serv. Univ. Medicina III, Serv. Anat. Patologica - H. Pulido Valente; Serv. Patologia - H.S.F. Xavier, Lisbon, Portugal

AIM: to study the prevalence of anti HCV core IgM antibodies (lg M) in chronic hepatitis C, in relation to epidemiological, biochemical data and to assess its significance as a predictor of agressive disease, by evaluation of the Knodell Index and a serum fibrogenesis marker - procollagen type III peptide (PIIlP) and follow up of the response to Interferon (IFN) therapy. METHODS : We studied 30 patients (10 IgM +; 20 IgM - ); (21 M; 9 F - mean age - 42,1 + 14,3 years) with chronic hepatitis C, diagnosed by persistent ALT elevation, presence of anti HVC IgG (RIBA I1/III) and viral RNA (PCR), and compatible histological diagnosis. Anti HVC-core IgM detection was performed by a EIA Kit (Abbot) and serum PIIIP was evaluated by RIA (Farmos Diagnostica) . We studied the relation between IgM positivity and response to IFN in 19 patients (6-1gM+; 13 IgM-) recruited for therapy (3 M.U,tiw, 12 months). RESULTS : lgM positivity occurred in 33.3% (10/30) of our patients; the comparison with IgM-patients (20/30) revealed that sporadic hepatitis (50% vs. 30%) and older patients - > 40 years (70% vs: 25%) were more frequent in the ]gM + population. There were no significant differences for ALT and GGT values and serum PIIIP range of variation, as well as for the relative frequency of histological diagnosis ( persistent h.-20% vs. 25%) ; active h. - 60% vs. 60%; cirrhosis - 20% vs. 15%). Knodell Index evaluation revealed a trend for higher level (mainly in the inflammation scores) in the lgM + group (7,4 _+ 4,2 vs. 6,1 _+ 48 - NS- t Stud). Complete biochemical response to IFN occurred in 66,7% (IgM +) vs. 76,9% (lgM -) of the treated patients (NS-Qsq), but the persistence of lgM positivity in 75% of the responders during therapy was associated with positive viral RNA. CONCLUSION : Anti HVC core lgM positivity was not significantly associated with specific epidemiological, biochemical or histological data; Knodell Index and PIIIP levels did not suggest a trend for evolution, but the initial response to IFN may be transient due to persistent viral replication.

1499 ORTHOTOPIC LIVER TRANSPLANTATION (OLT) IS SUCCESSFUL IN T H E M A N A G E M E N T OF HEPATIC DISEASE FOLLOWING BONE-MARROW TRANSPLANTATION (BMT) HR Rosen. P Martin. GJ Schiller, M Territo. DN Lewin. CR Shackleton, RW Busuttil. UCLA-Dumont Liver Transplantation Program, Div. of Hem/One, and Dept. of Pathology, UCLA School of Medicine, Los Angeles, CA.

Bone marrow transplantation (BMT) is successful and curative therapy for many primary hematological malignancies. However, hepatic dysfunction and failure are important causes of morbidity and mortality in this patient group following BMT. Hepatic failure can occur as a result of involvement by graft vs. host disease (GVHD) or as a result of veno-occlnsive disease (VOD). Therapies for these complications are often ineffective, especially for VOD as at least 50% who develop the condition die despite otherwise successful BMT. Accordingly, we have reviewed our center's experience with OLT to manage the hepatic complications of BMT. Between Feb. 1988 and Feb. 1995, 965 patients underwent OLT at our hospital. In 3 (0.3%), the indication for OLT was VOD or hepatic GVHD. Pt. 1 was a 34yo W with myelodysplastic syndrome who had an allogeneic BMT and developed VOD with hyperbilirubinemia (peak 37mg/dL), hepatic encephalopathy, hepatorenal syndrome and ascites with a 25% weight gain. OLT was performed on day +40 after BMT. By the fifth week liver and renal function were normal. She died 15 mos. later from acute leukemia. Pt. 2 is a 32yo M with acute myelogenous leukemia who underwent OLT for hepatic GVHD on day +330 after allogeneic BMT. 770 days after BMT, pt. has normal liver and marrow function. I t . 3 is a 35yo M with acute myelogenous leukemia who post-BMT developed cutaneous and mild gastrointestinal GVHD which responded to increased immunosuppression. VOD developed with Dx by liver biopsy and elevation of hepatic sinusoidal wedge pressure. Peak bill (44mg/dL), SGOT (1452 U/L) and weight gain (34%) predicted poor outcome. OLT was performed on day +43; he is well with normal liver graft 6 mos. post OLT. C O N C L U S I O N : Experience with liver transplantation for hepatic complications of BMT suggests OLT should be considered for BMT recipients who develop severe hepatic dysfunction. Longer follow-up will be needed to assess the optimal role of OLT post-BMT.

1500 COMPARISON OF TWO QUANTITATIVE COMPETITIVE HCV-RT- PCR ASSAYS. WK Roth, J-H Lee, B R~ster, S Zeuzem~ Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus and Medizinische Klinik II, Univ. of Frankfurt am Main, Germany.

A quantitative HCV RT-PCR assay established in our laboratory was compared with the Roche HCV Monitor ~ test kit for agreement of test results and intra-assay variability. Both assays rely on competitive reverse transcription and amplification of extracted RNA from patients' sere together with an internal RNA standard dedved from the 5'-NC region of HCV. Differentiation between HCV wildtype and standard amplification products is achieved by selective hybridization to a short sequence of exchanged nucleotides introduced into the respective standard RNAs. A panel of clinical serum samples (n=33), either undiluted or diluted, were quantitatively analyzed with both test systems. Both methods demonstrated substantial agreement between 1 x 103 and 5 x. 10 s HCV-RNA molecules / ml serum. The lower reproducible detection limit of both assays proved to be 1 x 103 molecules. Our in-house HCV RT-PCR assay measured up to 5 x 107 HCV-RNA molecules / ml in some sera However, the Roche HCV Monitor did not detect more than 2 x 106 molecules in any of the sera tested. After dilution of serum samples prior to testing approximately a 1/2-order of magnitude more HCV RNA molecules were deteced by the Roche HCV test kit in high copy number s e r e (> 5 x 105 RNA copies according to the in-house assay). By repeatedly testing the same samples with both assays in parallel, each assay revealed an intra-assay variability of one order of magnitude. Agreement of both tests was highly satisfactory in a range of 103 - 10 s genome equivalents / ml with a vadability of only one order of magnitude. With sera containing more than 5 x 105 copies /ml according to our in- house assay, results diverged in a non-acceptable range of two orders of magnitude.