- Email: [email protected]
544 Accuracy of two new predictive models in assessing fibrosis in chronic hepatitis C (CHC)
POSTERS
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THREE YEARS OF VERTICAL NETWORKING IN THE GERMAN N E T W O R K OF COMPETENCE ON VIRAL HEPATITIS: WHAT CAN WE LEARN FROM THE USAGE OF DIFFERENT INFORMATION TOOLS?
S. Meyer, M.R Manns, H. Wedemeyer, German Hep-Net. Department
Gastroenterology, Hepatology, and Endocrinology, Medical School Hannoue~ Hannover, Germany Treatment of patients with viral hepatitis is time consuming and sometimes complicated. Several offers of information as internet sites have been established, however systematic analyses of need and usage of these information platforms are lacking. The Competence Network on Viral Hepatitis (Hep-Net) has been established in 2002 and offers a telephone hotline, an e-mail service and a homepage with frequently asked questions (FAQs). We analysed the need and usage of the different Hep-Net media of vertical transfer of knowledge by the clustering of topics and key words of 2.470 telephone consultations (9% physicians and 91% patients), 961 e-mail consultations and 38.125 hits on FAQs on the Hep-Net homepage. Half of the registered hits on the internet FAQs-pages were related to questions on modes of HCV or HBV transmission. In contrast, patients used e-mails and the telephone hotline mainly for treatment of hepatitis Crelated issues. More than 46% of the physicians' questions referred to unclearness in indication of treatment. Questions on specific medical problems of individual patients and, in e-mails, also on legal issues played a major role for physicians. Many of these questions were not addressed in the current European and national guidelines. A detailed listing of unaddressed issues will be presented during the meeting. Patients most frequently used the telephone hotline (62% of all questions) while physicians asked most of their questions via the e-mail service for individual case management. Although male patients represent 55 60% of all patients with viral hepatitis, the telephone hotline was used in 55% by women indicating that the usage of different media addresses sex-specific needs. In summary, the Hep-Net vertical networking tools represent a fast, quality assured endorsement to the daily management of patients with viral hepatitis. The combination of internet, e-mail service and telephone hotline gives consideration to individual necessities of patients and physicians. However, the detailed analysis of usage also shows limitations of current guidelines which should be considered during updating.
[•
13C-METHACETIN BREATH TEST BY ONLINE M O L E C U L A R CORRELATION S P E C T R O S C O P Y COMPARED TO APRI AND LIVER B I O P S Y FOR THE A S S E S S M E N T OF FIBROSIS IN CHRONIC HEPATITIS C
O. Goetze, N. Selzner, A. Grau, M. Fried, T. Gerlach, M. Muellhaupt.
Division of Gastroenterology & Hepatology, University Hospital Zurich, Switzerland Background: Stable isotope breath tests have been developed for the noninvasive assessment of microsomal liver function in patients with chronic liver disease. Among different tests, the 13C-methacetin breath test (MBT) appears to be particularly suitable for the assessment of hepatic functional reserve. Aims: To assess prospectively the performance of MBT in patients with chronic hepatitis C infection using molecular correlation spectroscopy with a continuous, online, automatic breath collection and analysis system (Oridion BreathID, LTD Israel) and to compare MBT outcomes with aspartate transaminase to platelets ratio index (APRI). Methods: The METAVIR fibrosis score of a liver biopsy specimen obtained within six months of MBT was used as a "gold standard". 60 patients (37M, 48.1• BMI 24.2• kg/m2, AST 1.5• ALT 2.2• x upper limit of normal, platelet count 173• 103 /mm3 ) with chronic hepatitis C were studied (fibrosis stage F0, n=8; F1, n=22;
F2, n 11; F3, n 6; F4, n 13). After an overnight fast each patient received 75mg of 13C-methacetin dissolved in 100ml of water. The 13C/12C ratio was determined over 90 minutes by molecular correlation spectroscopy (1 sample/3 min) as delta over baseline (DOB[%o]) and was expressed as maximal (PDRmax[%/h]) as well as cumulative percentage dose of 13C recovered at 30 min (cPDR30[%]). Results: Both PDRmax and cPDR30 in patients with F ~<1 were higher than in patients with F/>2 (PDRmax: 29.6• vs 18.7• cPDR30:9.7• vs 5.7• p < 0.001). Mean areas under the receiver operating characteristic (ROC) curve of PDRmax, cPDR30 and APRI values were similar for F/> 2 (0.82, 0.87, 0.77) and for F/> 3 (0.93, 0.95, 0.88). For F 4 area under ROC was higher for cPDR30 than APRI (0.94 vs 0.81, p <0.05) but similar for PDRmax (0.91). Conclusions: MBT by continuous automatic molecular correlation spectroscopy is an easy to use and effective method for assessing liver fibrosis, with a better performance than APRI score for detection of severe stages of fibrosis and at least a similar performance to other reported non-invasive surrogate markers of liver fibrosis.
I•
A C C U R A C Y OF TWO NEW PREDICTIVE MODELS IN ASSESSING FIBROSIS IN CHRONIC HEPATITIS C (CHC)
S. Paggi 1, M. Fraquelli 1, D. Conte 1, M. Colombo 1, M. Vigan61 , C. Facciotto 1, R Dal Poggio 2, A. Colli 3. 1postgraduate School of
Gastroenterology, IRCCS Policlinico Hospital, Milan, Italy," 2Department of Internal Medicine, Hospital of Treviglio, Treviglio, Italy," 3Department of Internal Medicine/Hospital 'H. Manzoni'" Lecco, Italy Background: Assessment of fibrosis is basic in the management of CHC; histology represents the reference standard for severe fibrosis/cirrhosis, though invasive and with a high rate (~30%) of false negative results. Several algorithms, including laboratory tests (APRI, HALT-C), and the ultrasonographic sign of liver-surface-nodularity (LSN) have been proposed. As conditionally independent, laboratory scores and LSN can be used to construct new models. Aim: To assess the predictivity (discrimination and calibration power) and transferability (external validation) of these models (i.e. APRI+LSN and HALT-C+LSN). Patients and Methods: 430 consecutive CHC patients were studied: the internal cohort (#180) and the two external ones (#108 and #142) for the training and the external validation set, respectively. Histology represented the reference standard (METAVIR); F3 4 were considered together (severe fibrosis/cirrhosis), because of similar prognosis. To evaluate the clinical relevance of the models, three diagnostic levels of post-test (expected) probability of F3 4 were predefined: certain (~<10 or />90%), highly probable (75 90%) or still undefined (10 74%). Considering a pre-test probability of F3 4 of about 35%, the post-test one was calculated on the sequential application of the above scores and LSN (present or absent) and then compared with the observed one. Results: 37% of patients had F3 4. Calibration was similar for APRI and HALT-C, the former showing the best discrimination power. Patient distribution and the observed/expected (Obs/Exp) rate of F3 4 are given for APRI+LSN in Figure 1. No significant difference in the operative characteristics of the models in the three cohorts was observed. AFRI S C O R E Pts (%)
12 30
/\
LSN
neg
Pt~(%)
>2 i~
/\ pos
neg
pos
/\ ~g
'";" "\
P~ withy 3 4 0 b ~ (%)
~
61
Exlo(%)
~
i0-74
10-74
10-74
pos
05E Viral Hepatitis'
(f) Hepatitis' C
Conclusions: The APRI+LSN model obtained a high diagnostic accuracy,. given its calibration (comparable expected/observed frequency of F3 4) and adequate discrimination power, identifying comparable subgroups with different probability of F3 4. Thus, about 70% (see circles) of biopsies performed could be avoided. No significant difference between training and external validation sets was observed.
F
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C R Y O G L O B U L I N S IN PATIENTS WITH C H R O N I C HEPATITIS C VIRUS INFECTION: A S S O C I A T I O N S WITH A U T O I M M U N E D I S O R D E R S A N D B-CELL NON-HODGKIN'S LYMPHOMA
D.V. Petrova. K.G. Tchernev. Department of Internal Medicine and
Gastroenterology, University Hospital "Alexandrovska ", Sofia, Bulgaria Background: Hepatitis C virus (HCV) lymphotropism may explain a wide spectrum of HCV-related autoimmune and lymphoproliferative disorders, including cryoglobulinemia and B-cell non-Hodgkin's lymphoma (B-NHL). Aims: To assess the prevalence of cryoglobulins in patients with chronic HCV infection and to identify associations between HCVcryoglobulinemia, autoimmune disorders and B-NHL. Patients and Methods: 136 patients with chronic HCV infection were included in a case-controlled study. The prevalence of cryoglobulins, dermatologic, rheumatologic, neurologic, nephrologic, endocrine disorders, and B-NHL were assessed. Associations between HCV-cryoglobulinemia and epidemiology; demography; liver histology; biological and immunological abnormalities; clinical manifestations, and B-NHL were identified by univariate and multivariate logistic regression analyses. Results: Cryoglobulins were observed in 51/136 HCV-patients. Univariate analysis showed correlations between HCV-cryoglobulinemia and: the duration of infection >20 years (P 0.000); female sex (P 0.001); age >60 years (P 0.000); advanced liver fibrosis (P 0.000); and a history of blood transfusions in the past (P 0.000). Associations were found between HCV-cryoglobulinemia and the presence of: paresthesia (p 0.000); Raynaud's phenomenon (p 0.001); renal impairment (p 0.000); vasculitis of the lower extremities (p 0.000); diabetes (p 0.009); arthralgia (p 0.001); non-specific pneumofibrosis (p 0.015); B - N H L ( p 0.011); elevated total serum bilirubin (p 0.032); thrombocytopenia (p 0.000); anticardiolipin(p 0.011), antinuclear (p 0.012),antineutrophilcytoplasmic (p 0.002), antismooth muscle cells (p 0.000) autoantibodies; high levels of immunoglobulin A (p 0.021); low C3- (p 0.000), and low C4- (p 0.000) components of the complement. By multivariate analysis significant associations were identified between HCV-cryoglobulinemia and: female sex (p 0.029, OR 4.4, 95%CI 1.0 16.4); the duration of infection >20 years (p 0.000; OR 17.4, 95%CI 3.9 76.9); extensive liver fibrosis (p 0.056, OR 3.3, 95%CI 0.9 11.7); vasculitis of the lower extremities (p 0.003, OR 17.6, 95%CI 2.6 120.0); renal impairment (p 0.018,OR 5.7, 95%CI 1.3 22.1); B-NHL (p 0.0049, OR 12.6, 95%CI 1.0 156.0); and low C4-complement's component (p 0.001, OR 9.7, 95%CI 2.6 35.8). B-NHL were observed in 3/85 cryoglobulinsnegative (3.5%) and 9/51 cryoglobulins-positive (17.6%) patients. Three women with advanced liver fibrosis developed cryoglobulins and B-NHL during the follow-up. Conclusions: Cryoglobulins are observed in 37.5% of HCV-patients. The most frequent risk factors for the presence of HCV-cryoglobulinemia are: the female sex, the longer duration of infection and extensive liver fibrosis. Significant associations exist between HCV-cryoglobulinemia, vasculitis of the lower extremities, renal impairment and B-NHL.
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Clinical
Except therapy
$203
EARLY H C V - R N A DECLINE IN P E R I P H E R A L B L O O D M O N O N U C L E A R CELLS PREDICTS S V R V E R S U S RELAPSE IN C H R O N I C HEPATITIS C PATIENTS TREATED WITH PEGYLATED INTERFERON-~ PLUS RIBAVIRIN
R Pugnale 1, A.U. Neumann2, J.-M. Pawlotsky 3, S. Zeuzem4, F. Negro 1.
1University of Geneva Medical School, Geneva, Switzerland," 2Faculty of Life Seiences, Bar-Ilan University, Ramat-Gan 52900, Israel," 3Hdpital Henri Mondor Universite Paris' XII, Creteil, France," 4Saarland University Hospital, Homburg/Saar, Germany Assessment of HCV RNA kinetics in compartments other than plasma may be important to understand the correlates of sustained viral response (SVR) to therapy of chronic hepatitis C. We developed a real-time, TaqMan-based RT-PCR to quantify HCV RNA in peripheral blood mononuclear cells (PBMC). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was co-amplified in a multiplex reaction. Linearity between input RNA and CT values was observed over 6 logs (R2 ~>0.99). Lower sensitivity level was 4 viral copies/reaction, with high accuracy (CV ~<3.94%) and reproducibility (CV ~<2.20%). We assessed HCV RNA kinetics in plasma and PBMC of 50 chronic hepatitis C patients treated for 24 48 weeks with pegylated interferon-~-2a and ribavirin. All were early virological responders (<50 IU/ml HCV-RNA in plasma at 12 weeks) but 22 relapsed (REL) after treatment while 28 had SVR. Of those, 9 REL patients and 18 with SVR had HCV genotype 1 and 48 weeks of treatment. HCV RNA decline in PBMC correlated (R 0.8, p <0.003) with that in plasma at days 8 and 22 of therapy, although 20% of patients had >1 log difference in the declines. Viral kinetic slopes in PBMC and plasma were highly correlated in 12 of 16 patients that had samples available also at days 1 and 4, including a 0.5log rebound between days 4 to 8 in 38% of patients. HCV RNA decline in PBMC (but not in plasma) at day 8 was significantly (p 0.007) larger in SVR (mean 2.5 log) versus REL (0.9log) genotype 1 patients treated for 48 weeks. All (n 8) patients with >3.0 log HCV RNA decline in PBMC became SVR as compared to none of the patients with <0.5 log decline. HCV RNA kinetics in PBMC during treatment with pegylated interferon-~-2a and ribavirin follows in general the decline in plasma, indicating similar anti-viral effectiveness in that compartment. However, differences in plasma and PBMC kinetics in some patients may indicate different compartment dynamics. Assessment of HCV RNA decline in PBMC may allow early prediction of SVR versus relapse.
D E M I O L O G Y A N D N A T U R A L C O U R S E OF HEPATITIS C F•-I EINP IGREECE: RESULTS OF THE NATIONWIDE H E P N E T G R E E C E C O H O R T STUDY
M. Raptopouloul~ D. Tzoumakliotis2, G. Nikolopoulou 3, A. Skoutelis4, G. Dalekos 5, M. Dimopoulou6, K. Angelidou7, A. Avgerinos8, G. Chatzis 9, S. Manolakopoulos 2. 12nd Dpt of Medicine, Thessaloniki
University Medical School, Hippokration Hospital, Greece," 2Dpt of Gastroenterology, Policliniki, General Hospital, Athens, Greece," 3Hellenic Center for Disease Control, 45th Dpt of Medicine, Evangelismos Hospital, Athens, Greece," 5Dpt of Medicine, Thessalia University Medical School, Greece," 6Dpt of Medicine, Hippokration General Hospital, Athens, Greece," 7Dpt of Hygiene & Epidemiology, Athens University Medical School, Greece," 82nd Dpt of Gastroenterology, Evangelismos General Hospital, Athens, Greece," 92nd Dpt of Medical Physiology, Athens University Medical School, Greece Background and Aim: HEPNET GREECE is an ongoing nationwide retrospective-prospective, government sponsored, study, aimed to evaluate the epidemiology and natural course of chronic HCV infection in Greece as well as their longitudinal changes. In this initial report, we describe the patient baseline demographic, clinical and virological characteristics.
$202
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THREE YEARS OF VERTICAL NETWORKING IN THE GERMAN N E T W O R K OF COMPETENCE ON VIRAL HEPATITIS: WHAT CAN WE LEARN FROM THE USAGE OF DIFFERENT INFORMATION TOOLS?
S. Meyer, M.R Manns, H. Wedemeyer, German Hep-Net. Department
Gastroenterology, Hepatology, and Endocrinology, Medical School Hannoue~ Hannover, Germany Treatment of patients with viral hepatitis is time consuming and sometimes complicated. Several offers of information as internet sites have been established, however systematic analyses of need and usage of these information platforms are lacking. The Competence Network on Viral Hepatitis (Hep-Net) has been established in 2002 and offers a telephone hotline, an e-mail service and a homepage with frequently asked questions (FAQs). We analysed the need and usage of the different Hep-Net media of vertical transfer of knowledge by the clustering of topics and key words of 2.470 telephone consultations (9% physicians and 91% patients), 961 e-mail consultations and 38.125 hits on FAQs on the Hep-Net homepage. Half of the registered hits on the internet FAQs-pages were related to questions on modes of HCV or HBV transmission. In contrast, patients used e-mails and the telephone hotline mainly for treatment of hepatitis Crelated issues. More than 46% of the physicians' questions referred to unclearness in indication of treatment. Questions on specific medical problems of individual patients and, in e-mails, also on legal issues played a major role for physicians. Many of these questions were not addressed in the current European and national guidelines. A detailed listing of unaddressed issues will be presented during the meeting. Patients most frequently used the telephone hotline (62% of all questions) while physicians asked most of their questions via the e-mail service for individual case management. Although male patients represent 55 60% of all patients with viral hepatitis, the telephone hotline was used in 55% by women indicating that the usage of different media addresses sex-specific needs. In summary, the Hep-Net vertical networking tools represent a fast, quality assured endorsement to the daily management of patients with viral hepatitis. The combination of internet, e-mail service and telephone hotline gives consideration to individual necessities of patients and physicians. However, the detailed analysis of usage also shows limitations of current guidelines which should be considered during updating.
[•
13C-METHACETIN BREATH TEST BY ONLINE M O L E C U L A R CORRELATION S P E C T R O S C O P Y COMPARED TO APRI AND LIVER B I O P S Y FOR THE A S S E S S M E N T OF FIBROSIS IN CHRONIC HEPATITIS C
O. Goetze, N. Selzner, A. Grau, M. Fried, T. Gerlach, M. Muellhaupt.
Division of Gastroenterology & Hepatology, University Hospital Zurich, Switzerland Background: Stable isotope breath tests have been developed for the noninvasive assessment of microsomal liver function in patients with chronic liver disease. Among different tests, the 13C-methacetin breath test (MBT) appears to be particularly suitable for the assessment of hepatic functional reserve. Aims: To assess prospectively the performance of MBT in patients with chronic hepatitis C infection using molecular correlation spectroscopy with a continuous, online, automatic breath collection and analysis system (Oridion BreathID, LTD Israel) and to compare MBT outcomes with aspartate transaminase to platelets ratio index (APRI). Methods: The METAVIR fibrosis score of a liver biopsy specimen obtained within six months of MBT was used as a "gold standard". 60 patients (37M, 48.1• BMI 24.2• kg/m2, AST 1.5• ALT 2.2• x upper limit of normal, platelet count 173• 103 /mm3 ) with chronic hepatitis C were studied (fibrosis stage F0, n=8; F1, n=22;
F2, n 11; F3, n 6; F4, n 13). After an overnight fast each patient received 75mg of 13C-methacetin dissolved in 100ml of water. The 13C/12C ratio was determined over 90 minutes by molecular correlation spectroscopy (1 sample/3 min) as delta over baseline (DOB[%o]) and was expressed as maximal (PDRmax[%/h]) as well as cumulative percentage dose of 13C recovered at 30 min (cPDR30[%]). Results: Both PDRmax and cPDR30 in patients with F ~<1 were higher than in patients with F/>2 (PDRmax: 29.6• vs 18.7• cPDR30:9.7• vs 5.7• p < 0.001). Mean areas under the receiver operating characteristic (ROC) curve of PDRmax, cPDR30 and APRI values were similar for F/> 2 (0.82, 0.87, 0.77) and for F/> 3 (0.93, 0.95, 0.88). For F 4 area under ROC was higher for cPDR30 than APRI (0.94 vs 0.81, p <0.05) but similar for PDRmax (0.91). Conclusions: MBT by continuous automatic molecular correlation spectroscopy is an easy to use and effective method for assessing liver fibrosis, with a better performance than APRI score for detection of severe stages of fibrosis and at least a similar performance to other reported non-invasive surrogate markers of liver fibrosis.
I•
A C C U R A C Y OF TWO NEW PREDICTIVE MODELS IN ASSESSING FIBROSIS IN CHRONIC HEPATITIS C (CHC)
S. Paggi 1, M. Fraquelli 1, D. Conte 1, M. Colombo 1, M. Vigan61 , C. Facciotto 1, R Dal Poggio 2, A. Colli 3. 1postgraduate School of
Gastroenterology, IRCCS Policlinico Hospital, Milan, Italy," 2Department of Internal Medicine, Hospital of Treviglio, Treviglio, Italy," 3Department of Internal Medicine/Hospital 'H. Manzoni'" Lecco, Italy Background: Assessment of fibrosis is basic in the management of CHC; histology represents the reference standard for severe fibrosis/cirrhosis, though invasive and with a high rate (~30%) of false negative results. Several algorithms, including laboratory tests (APRI, HALT-C), and the ultrasonographic sign of liver-surface-nodularity (LSN) have been proposed. As conditionally independent, laboratory scores and LSN can be used to construct new models. Aim: To assess the predictivity (discrimination and calibration power) and transferability (external validation) of these models (i.e. APRI+LSN and HALT-C+LSN). Patients and Methods: 430 consecutive CHC patients were studied: the internal cohort (#180) and the two external ones (#108 and #142) for the training and the external validation set, respectively. Histology represented the reference standard (METAVIR); F3 4 were considered together (severe fibrosis/cirrhosis), because of similar prognosis. To evaluate the clinical relevance of the models, three diagnostic levels of post-test (expected) probability of F3 4 were predefined: certain (~<10 or />90%), highly probable (75 90%) or still undefined (10 74%). Considering a pre-test probability of F3 4 of about 35%, the post-test one was calculated on the sequential application of the above scores and LSN (present or absent) and then compared with the observed one. Results: 37% of patients had F3 4. Calibration was similar for APRI and HALT-C, the former showing the best discrimination power. Patient distribution and the observed/expected (Obs/Exp) rate of F3 4 are given for APRI+LSN in Figure 1. No significant difference in the operative characteristics of the models in the three cohorts was observed. AFRI S C O R E Pts (%)
12 30
/\
LSN
neg
Pt~(%)
>2 i~
/\ pos
neg
pos
/\ ~g
'";" "\
P~ withy 3 4 0 b ~ (%)
~
61
Exlo(%)
~
i0-74
10-74
10-74
pos
05E Viral Hepatitis'
(f) Hepatitis' C
Conclusions: The APRI+LSN model obtained a high diagnostic accuracy,. given its calibration (comparable expected/observed frequency of F3 4) and adequate discrimination power, identifying comparable subgroups with different probability of F3 4. Thus, about 70% (see circles) of biopsies performed could be avoided. No significant difference between training and external validation sets was observed.
F
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'
I
C R Y O G L O B U L I N S IN PATIENTS WITH C H R O N I C HEPATITIS C VIRUS INFECTION: A S S O C I A T I O N S WITH A U T O I M M U N E D I S O R D E R S A N D B-CELL NON-HODGKIN'S LYMPHOMA
D.V. Petrova. K.G. Tchernev. Department of Internal Medicine and
Gastroenterology, University Hospital "Alexandrovska ", Sofia, Bulgaria Background: Hepatitis C virus (HCV) lymphotropism may explain a wide spectrum of HCV-related autoimmune and lymphoproliferative disorders, including cryoglobulinemia and B-cell non-Hodgkin's lymphoma (B-NHL). Aims: To assess the prevalence of cryoglobulins in patients with chronic HCV infection and to identify associations between HCVcryoglobulinemia, autoimmune disorders and B-NHL. Patients and Methods: 136 patients with chronic HCV infection were included in a case-controlled study. The prevalence of cryoglobulins, dermatologic, rheumatologic, neurologic, nephrologic, endocrine disorders, and B-NHL were assessed. Associations between HCV-cryoglobulinemia and epidemiology; demography; liver histology; biological and immunological abnormalities; clinical manifestations, and B-NHL were identified by univariate and multivariate logistic regression analyses. Results: Cryoglobulins were observed in 51/136 HCV-patients. Univariate analysis showed correlations between HCV-cryoglobulinemia and: the duration of infection >20 years (P 0.000); female sex (P 0.001); age >60 years (P 0.000); advanced liver fibrosis (P 0.000); and a history of blood transfusions in the past (P 0.000). Associations were found between HCV-cryoglobulinemia and the presence of: paresthesia (p 0.000); Raynaud's phenomenon (p 0.001); renal impairment (p 0.000); vasculitis of the lower extremities (p 0.000); diabetes (p 0.009); arthralgia (p 0.001); non-specific pneumofibrosis (p 0.015); B - N H L ( p 0.011); elevated total serum bilirubin (p 0.032); thrombocytopenia (p 0.000); anticardiolipin(p 0.011), antinuclear (p 0.012),antineutrophilcytoplasmic (p 0.002), antismooth muscle cells (p 0.000) autoantibodies; high levels of immunoglobulin A (p 0.021); low C3- (p 0.000), and low C4- (p 0.000) components of the complement. By multivariate analysis significant associations were identified between HCV-cryoglobulinemia and: female sex (p 0.029, OR 4.4, 95%CI 1.0 16.4); the duration of infection >20 years (p 0.000; OR 17.4, 95%CI 3.9 76.9); extensive liver fibrosis (p 0.056, OR 3.3, 95%CI 0.9 11.7); vasculitis of the lower extremities (p 0.003, OR 17.6, 95%CI 2.6 120.0); renal impairment (p 0.018,OR 5.7, 95%CI 1.3 22.1); B-NHL (p 0.0049, OR 12.6, 95%CI 1.0 156.0); and low C4-complement's component (p 0.001, OR 9.7, 95%CI 2.6 35.8). B-NHL were observed in 3/85 cryoglobulinsnegative (3.5%) and 9/51 cryoglobulins-positive (17.6%) patients. Three women with advanced liver fibrosis developed cryoglobulins and B-NHL during the follow-up. Conclusions: Cryoglobulins are observed in 37.5% of HCV-patients. The most frequent risk factors for the presence of HCV-cryoglobulinemia are: the female sex, the longer duration of infection and extensive liver fibrosis. Significant associations exist between HCV-cryoglobulinemia, vasculitis of the lower extremities, renal impairment and B-NHL.
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Clinical
Except therapy
$203
EARLY H C V - R N A DECLINE IN P E R I P H E R A L B L O O D M O N O N U C L E A R CELLS PREDICTS S V R V E R S U S RELAPSE IN C H R O N I C HEPATITIS C PATIENTS TREATED WITH PEGYLATED INTERFERON-~ PLUS RIBAVIRIN
R Pugnale 1, A.U. Neumann2, J.-M. Pawlotsky 3, S. Zeuzem4, F. Negro 1.
1University of Geneva Medical School, Geneva, Switzerland," 2Faculty of Life Seiences, Bar-Ilan University, Ramat-Gan 52900, Israel," 3Hdpital Henri Mondor Universite Paris' XII, Creteil, France," 4Saarland University Hospital, Homburg/Saar, Germany Assessment of HCV RNA kinetics in compartments other than plasma may be important to understand the correlates of sustained viral response (SVR) to therapy of chronic hepatitis C. We developed a real-time, TaqMan-based RT-PCR to quantify HCV RNA in peripheral blood mononuclear cells (PBMC). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was co-amplified in a multiplex reaction. Linearity between input RNA and CT values was observed over 6 logs (R2 ~>0.99). Lower sensitivity level was 4 viral copies/reaction, with high accuracy (CV ~<3.94%) and reproducibility (CV ~<2.20%). We assessed HCV RNA kinetics in plasma and PBMC of 50 chronic hepatitis C patients treated for 24 48 weeks with pegylated interferon-~-2a and ribavirin. All were early virological responders (<50 IU/ml HCV-RNA in plasma at 12 weeks) but 22 relapsed (REL) after treatment while 28 had SVR. Of those, 9 REL patients and 18 with SVR had HCV genotype 1 and 48 weeks of treatment. HCV RNA decline in PBMC correlated (R 0.8, p <0.003) with that in plasma at days 8 and 22 of therapy, although 20% of patients had >1 log difference in the declines. Viral kinetic slopes in PBMC and plasma were highly correlated in 12 of 16 patients that had samples available also at days 1 and 4, including a 0.5log rebound between days 4 to 8 in 38% of patients. HCV RNA decline in PBMC (but not in plasma) at day 8 was significantly (p 0.007) larger in SVR (mean 2.5 log) versus REL (0.9log) genotype 1 patients treated for 48 weeks. All (n 8) patients with >3.0 log HCV RNA decline in PBMC became SVR as compared to none of the patients with <0.5 log decline. HCV RNA kinetics in PBMC during treatment with pegylated interferon-~-2a and ribavirin follows in general the decline in plasma, indicating similar anti-viral effectiveness in that compartment. However, differences in plasma and PBMC kinetics in some patients may indicate different compartment dynamics. Assessment of HCV RNA decline in PBMC may allow early prediction of SVR versus relapse.
D E M I O L O G Y A N D N A T U R A L C O U R S E OF HEPATITIS C F•-I EINP IGREECE: RESULTS OF THE NATIONWIDE H E P N E T G R E E C E C O H O R T STUDY
M. Raptopouloul~ D. Tzoumakliotis2, G. Nikolopoulou 3, A. Skoutelis4, G. Dalekos 5, M. Dimopoulou6, K. Angelidou7, A. Avgerinos8, G. Chatzis 9, S. Manolakopoulos 2. 12nd Dpt of Medicine, Thessaloniki
University Medical School, Hippokration Hospital, Greece," 2Dpt of Gastroenterology, Policliniki, General Hospital, Athens, Greece," 3Hellenic Center for Disease Control, 45th Dpt of Medicine, Evangelismos Hospital, Athens, Greece," 5Dpt of Medicine, Thessalia University Medical School, Greece," 6Dpt of Medicine, Hippokration General Hospital, Athens, Greece," 7Dpt of Hygiene & Epidemiology, Athens University Medical School, Greece," 82nd Dpt of Gastroenterology, Evangelismos General Hospital, Athens, Greece," 92nd Dpt of Medical Physiology, Athens University Medical School, Greece Background and Aim: HEPNET GREECE is an ongoing nationwide retrospective-prospective, government sponsored, study, aimed to evaluate the epidemiology and natural course of chronic HCV infection in Greece as well as their longitudinal changes. In this initial report, we describe the patient baseline demographic, clinical and virological characteristics.