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272A AASLD ABSTRACTS HEPATOLOGY October 1995 661 CLINICAL AND HISTOLOGICAL FEA~L~ES IN ANTI HCV RIBA INDE TERMINATE PATIENTS WITH NORMAL ALT.R Diago,P Carbonell, C Gonzalez,R zapater,R Cors,P Rivera,C Tuset,J Villalba Hepatology and Inmunology Sections.Hospital General Universitary.Valencia. Spain. The aim is to determine the clinical and histological findings in patients with anti HCV RIBA 2 indeterminate and normal ALT. We studied 81 patients(39 men and 42 women,age 41.l,range 19-64) .In each patient,the clinical and epidemiological data were collected.Liver function test,anti HIV,markers of hepatitis B~RNA-VHC(by PCR),anti HCV RIBA 3 and liver biopsy were performed in all the patients.We compared histological findings according to the results of PCR-VHC (+/-) ,the antibody band positive in RIBA 2 and the RIBA 3 results ( +/-/indetemninate). ~TH:Previous transfusion was present in 18.5%(15/81) and without parenteral antecedents in 72.8%(59/81).ALT le vels were persistently normal in all patients,and they were HIV and HBsAg negative.Previous HBV infection was detected in 22.8%.Histological diagnoses were:Chronic hepatitis (CAH or CPH) in 49%(40/81),Fatty liver in 8.6%(7/81),Minimal changes in 31%(25/81) and normal liver in ii%(9/81). RNA-VHC (PCR) was positive in 8 patients:2 CPE,3 CAH,3 MC. Histological diagnoses in the 73 PCR negative patients were 27 CPH(37%),7CAH(9.6%),7 FL(9.6%),I C~(1.3%),22 MC(30%) and 9 normal liver(12.3%). The RIBA 3 was positive in 10% of RIBA 2 positive patients, negative in i0% and indeterminate in 80%. CON<X~SIONS:Only 27% of RIBA 2 indeterminate patients had a parenteral risk of HCV acquisition.Half of the patients with RIBA 2 indeterminate had chronic hepatitis and only 8.6% had a normal liver.RNA (by PCR) was detected in 10%. There is no relationship between the band of RIBA 2 inde- terminate and the severity of liver disease. Eighty per cent of RIBA 2 indeterminate patients were RIBA 3 indeterminate. 662 HEPATITIS C VIRUS GENOTYPES, RNA TITER AND LIVER HISTOLOGY IN VOLUNTEER BLOOD DONORS WITH DIFFERENT ALANINE AMINOTRANSFERASE PROFILE A. Rossini: A. Rava~-,i*. L. Biasi. G.B. Gazzola°. E. Agostinelli °, E. Radaefi. E. Cariani* III Department of Internal Medicine, Hospital of Brescia, *III Laboratory of Clinical Chemistry, Hospital of Brescia, °Blood Transfusion Service, Hospital of Chiari, Italy B~ckground: Little is known about the viral genotypes, the levels of viremia and the severity of liver lesions in blood donors with HCV infection and persistently normal alanine aminotransferase (ALl) levels. Study design and methods: We analyzed HCV genotype and RNA titer in 33 volunteer blood donors, 19 with persistently normal and 14 with raised ALl" levels. Seventeen donors with normal ALT and all donors with raised ALT underwent liver biopsy and evaluation of the histological activity index (HAI). Results; Genotype 2 was detected in most donors with normal ALT, • whereas genotype 1 was more frequent among donors with raised ALT (p<0.01). HCV RNA titer, determined by competitive PCR, was higher in donors with raised ALT than in those with normal ALT (median 8.2 log copies/ml, range 6.1-8.85, vs median 7.4, range 4.95:8.6, p=0.01): The scores for portal inflammation and for fibrosis in the HAI were higher in donors with increased ALT (p<0.05 and p<0.01). HCV genotype had no statistical relationship with RNA titer or with liver histology. The score for periportal necrosis was correlated with the viral titer (p<0.01). Conclusion: Both the infecting genotype and the levels of hepatitis C virus replication were independently associated with the ALT profile. The severity of portal inflammation and fibrosis was higher in donors with raised ALT, and the rate of viral replication was correlated with the degree of periportal necrosis. 663 HCV-VIREMIA IN SERUM AND LIVER TISSUE OF ANTI-HCV POSITIVE SUBJECTS: CORRELATION WITH ALT AND LIVER HISTOLOGY. M. Persico,*V. Nigro, E__ a. Persico, L. Gesu~, S. Conte, I. de Sio, S. Gentile and R. Torella~-- Internal--Medicine-and Hepatology, *Patologia Generale-II Univ of Naples, Italy. We studied 30 HCV-RNA positive subjects, 15 with high ALT levels and 15 with normal ALT who underwent ultrasound guided liver biopsy.All the subjects were comparable for age(47 yrs, range 32-63) and sex (F/M: 6/9 and 7/8). HCV-viremia was assessed on serum and liver tissue according to the followi~ng method. Th~ most conserved region(5')of HCV-RNA retrotranscribed and amplified with outer primers and cloned. To this product the middle 70 bp of exogenous DNA were added and different dilutions of this longer product were used for competitive PCR.Liver tissue HCV-RNA was significantly correlated to serum HCV-RNA in "symptomatic" patients(M:l~ copies of genome/ml,range 10%-109vs. M:10~copies of genome/ml,range 10L-10~; r=0.627 p<0.01). No significantly correlation was rather found in "Asymptomatic" subjects.No difference in HCV-RNA tissue levels was detected between the two groups whereas serum HCV-RNA levels were significantly different (M:10%,range 750- i0 y copies of genome /ml vs. M:IO~, range i0% -108 copies of genome/ml p<O.01).Liver histology was comparable in the two groups and ALT serum levels significantly related to HCV-Viremia. CONCLUSIONS:HCV-viremia does not parallel tissue levels of HCV-RNA indicating that virus C replication might also be identified in areas other than liver. Serum HCV-viremia seems to be the only discriminating value among different phases of HCV related-CH. 664 SERUM ASPARTATEAMINOTRANSFERASE (AST) VALUES AS A USEFUL PREDICTOR FOR THE HISTOLOGIC FEATURES OF CHRONIC HEPATITIS C INFECTION IN ADULTS. N. ~sv and G.Y..Minuk. Liver Diseases Unit and Liver Diseases Research Laboratory, Departments of Medicine and Pharmacology, University of Manitoba, Winnipeg, Manitoba. We assessed the predictive value of age, gender, route of transmission, extent of steatosis, alcohol consumption and aminotransferase vatues (ALT, AST) on the histologic findings of 79 adult patients with chronic hepatitis C viral infections. The mean (+ SD) age of the patient population was 43.5+10.8 years of which 60% were male. The route of transmission was considered to be parenteral drugs in 56%, previous blood transfusions in 32% and various non-parenteral routes in 13%. Results: The mean histologic activity score of the group as described by Desmet et al was 3.54-0.8 and fibrosis score 1.5+0.4. The extent of inflammation correlated with fibrosis (r = 0.72). By multivariate stepwise regression analyses, the AST emerged as the most important predictor variable of histologic activity (p < O.O0001 ). When overall histologic activity was separated into portal inflammation, piecemeal necrosis and Iobular activity, significant correlations existed between AST values and portal inflammation (p < 0.0001) and piecemeal necrosis (p < 0.005) but not Iobular activity (p = 0.9) A strong correlation was also observed between AST values and the extent of hepatic fibrosis (p < 0.0001 ). On the other hand, ALT values did not correlate with histologic activity but did correlate with the extent of hepatic fibrosis (p < 0.01 ). There were no significant correlations between age, gender, route of transmission, steatosis or alcohol consumption with the extent of histologic activity or fibrosis. In conclusion, AST values correlate well with two of three features of hepatic inflammation and with the extent of hepatic fibrosis. These findings suggest that AST values should be considered in decisions regarding the need for liver biopsy and treatment in patients with chronic hepatitis C viral infections.

Clinical and histological features in anti HCV RIBA indeterminate patients with normal ALT Hepatology and Inmunology Sections.Hospital General Universitary.Valencia.Spain

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Page 1: Clinical and histological features in anti HCV RIBA indeterminate patients with normal ALT  Hepatology and Inmunology Sections.Hospital General Universitary.Valencia.Spain

2 7 2 A A A S L D A B S T R A C T S HEPATOLOGY October 1995

661 CLINICAL AND HISTOLOGICAL FEA~L~ES IN ANTI HCV RIBA INDE TERMINATE PATIENTS WITH NORMAL ALT.R Diago,P Carbonell, C Gonzalez,R zapater,R Cors,P Rivera,C Tuset,J Villalba Hepatology and Inmunology Sections.Hospital General Universitary. Valencia. Spain.

The aim is to determine the clinical and histological findings in patients with anti HCV RIBA 2 indeterminate and normal ALT. We studied 81 patients(39 men and 42 women,age 41.l,range 19-64) .In each patient,the clinical and epidemiological data were collected.Liver function test,anti HIV,markers of hepatitis B~RNA-VHC(by PCR),anti HCV RIBA 3 and liver biopsy were performed in all the patients.We compared histological findings according to the results of PCR-VHC (+/-) ,the antibody band positive in RIBA 2 and the RIBA 3 results ( +/-/indetemninate). ~TH:Previous transfusion was present in 18.5%(15/81) and without parenteral antecedents in 72.8%(59/81).ALT le vels were persistently normal in all patients,and they were HIV and HBsAg negative.Previous HBV infection was detected in 22.8%.Histological diagnoses were:Chronic hepatitis (CAH or CPH) in 49%(40/81),Fatty liver in 8.6%(7/81),Minimal changes in 31%(25/81) and normal liver in ii%(9/81). RNA-VHC (PCR) was positive in 8 patients:2 CPE,3 CAH,3 MC. Histological diagnoses in the 73 PCR negative patients were 27 CPH(37%),7CAH(9.6%),7 FL(9.6%),I C~(1.3%),22 MC(30%) and 9 normal liver(12.3%). The RIBA 3 was positive in 10% of RIBA 2 positive patients, negative in i0% and indeterminate in 80%. CON<X~SIONS:Only 27% of RIBA 2 indeterminate patients had a parenteral risk of HCV acquisition.Half of the patients with RIBA 2 indeterminate had chronic hepatitis and only 8.6% had a normal liver.RNA (by PCR) was detected in 10%. There is no relationship between the band of RIBA 2 inde- terminate and the severity of liver disease. Eighty per cent of RIBA 2 indeterminate patients were RIBA 3 indeterminate.

662 HEPATITIS C VIRUS GENOTYPES, RNA TITER AND LIVER HISTOLOGY IN VOLUNTEER BLOOD DONORS WITH DIFFERENT ALANINE AMINOTRANSFERASE PROFILE A. Rossini: A. Rava~-,i*. L. Biasi. G.B. Gazzola °. E. Agostinelli °, E. Radaefi. E. Cariani* III Department of Internal Medicine, Hospital of Brescia, *III Laboratory of Clinical Chemistry, Hospital of Brescia, °Blood Transfusion Service, Hospital of Chiari, Italy

B~ckground: Little is known about the viral genotypes, the levels of viremia and the severity of liver lesions in blood donors with HCV infection and persistently normal alanine aminotransferase (ALl) levels. Study design and methods: We analyzed HCV genotype and RNA titer in 33 volunteer blood donors, 19 with persistently normal and 14 with raised ALl" levels. Seventeen donors with normal ALT and all donors with raised ALT underwent liver biopsy and evaluation of the histological activity index (HAI). Results; Genotype 2 was detected in most donors with normal ALT,

• whereas genotype 1 was more frequent among donors with raised ALT (p<0.01). HCV RNA titer, determined by competitive PCR, was higher in donors with raised ALT than in those with normal ALT (median 8.2 log copies/ml, range 6.1-8.85, vs median 7.4, range 4.95:8.6, p=0.01): The scores for portal inflammation and for fibrosis in the HAI were higher in donors with increased ALT (p<0.05 and p<0.01). HCV genotype had no statistical relationship with RNA titer or with liver histology. The score for periportal necrosis was correlated with the viral titer (p<0.01). Conclusion: Both the infecting genotype and the levels of hepatitis C virus replication were independently associated with the ALT profile. The severity of portal inflammation and fibrosis was higher in donors with raised ALT, and the rate of viral replication was correlated with the degree of periportal necrosis.

663 HCV-VIREMIA IN SERUM AND LIVER TISSUE OF ANTI-HCV POSITIVE SUBJECTS: CORRELATION WITH ALT AND LIVER HISTOLOGY. M. Persico,*V. Nigro, E__ a. Persico, L. Gesu~, S. Conte, I. de Sio, S. Gentile and R. Torella~-- Internal--Medicine-and Hepatology, *Patologia Generale-II Univ of Naples, Italy. We studied 30 HCV-RNA positive subjects, 15 with high ALT levels and 15 with normal ALT who underwent ultrasound guided liver biopsy.All the

subjects were comparable for age(47 yrs, range 32-63) and sex (F/M: 6/9 and 7/8). HCV-viremia was assessed on serum and liver tissue according to the followi~ng method. Th~ most conserved region(5')of HCV-RNA retrotranscribed and amplified with outer primers and cloned. To this product the middle 70 bp of exogenous DNA were added and different dilutions of this longer product were used for competitive PCR.Liver tissue HCV-RNA was significantly correlated to serum HCV-RNA in "symptomatic" patients(M:l~ copies of genome/ml,range 10%-109vs. M:10~copies of genome/ml,range 10L-10~; r=0.627 p<0.01). No significantly correlation was rather found in "Asymptomatic" subjects.No difference in HCV-RNA tissue levels was detected between the two groups whereas serum HCV-RNA levels were significantly different (M:10%,range 750- i0 y copies of genome /ml vs. M:IO~, range i0% -108 copies of genome/ml p<O.01).Liver histology was comparable in the two groups and ALT serum levels significantly related to HCV-Viremia. CONCLUSIONS:HCV-viremia does not parallel tissue levels of HCV-RNA indicating that virus C replication might also be identified in areas other than liver. Serum HCV-viremia seems to be the only discriminating value among different phases of HCV related-CH.

664 SERUM ASPARTATEAMINOTRANSFERASE (AST) VALUES AS A USEFUL PREDICTOR FOR THE HISTOLOGIC FEATURES OF CHRONIC HEPATITIS C INFECTION IN ADULTS. N. ~sv and G.Y..Minuk. Liver Diseases Unit and Liver Diseases Research Laboratory, Departments of Medicine and Pharmacology, University of Manitoba, Winnipeg, Manitoba.

We assessed the predictive value of age, gender, route of transmission, extent of steatosis, alcohol consumption and aminotransferase vatues (ALT, AST) on the histologic findings of 79 adult patients with chronic hepatitis C viral infections. The mean ( + SD) age of the patient population was 43.5+10.8 years of which 60% were male. The route of transmission was considered to be parenteral drugs in 56%, previous blood transfusions in 32% and various non-parenteral routes in 13%. Results: The mean histologic activity score of the group as described by Desmet et al was 3.54-0.8 and fibrosis score 1.5+0.4. The extent of inflammation correlated with fibrosis (r = 0.72). By multivariate stepwise regression analyses, the AST emerged as the most important predictor variable of histologic activity (p < O.O0001 ). When overall histologic activity was separated into portal inflammation, piecemeal necrosis and Iobular activity, significant correlations existed between AST values and portal inflammation (p < 0.0001) and piecemeal necrosis (p < 0.005) but not Iobular activity (p = 0.9) A strong correlation was also observed between AST values and the extent of hepatic fibrosis (p < 0.0001 ). On the other hand, ALT values did not correlate with histologic activity but did correlate with the extent of hepatic fibrosis (p < 0.01 ). There were no significant correlations between age, gender, route of transmission, steatosis or alcohol consumption with the extent of histologic activity or fibrosis. In conclusion, AST values correlate well with two of three features of hepatic inflammation and with the extent of hepatic fibrosis. These findings suggest that AST values should be considered in decisions regarding the need for liver biopsy and treatment in patients with chronic hepatitis C viral infections.