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Correlation between symptoms, aminotransferases and liver histology in I.V.D.A. hepatitis C pts
A1064
AASLD ABSTRACTS
Correlation between Symptoms, Aminotransferases Liver Histology in I . V . D . A . H e p a t i t i s C pts.
GASTROENTEROLOGY,VoI. IO8, No. 4
and
RI.Farrell.I.Khan.M.Malonev.J.Farrell.GSA.MeDonald*.PWN.Keelin ~. Dept, of Gastroenterology & Pathology*,gt.James's Hospital, Dublin 8, Ireland. Object: To assess the correlation between the clinical, biochemical and histologieal activity in intravenous drug related Hepatitis C pts. Patients:47 IVDA's who were diagnosed HCV.positive according to the Ortho EIA,UBI EIA and RIBA '3 tests were referred for liver biopsy. The male:female ratio was 2il,mean age was 28.Syrs., mean interval betweenHCV testing and liver biopsy was 5.1 mths.with a mean length of IVDA.preceding HCV testing of 7.6 yrs. Pts. with an alcohol consumption >14u./wk. for females .and >21u./wk.for males was excluded from review. All pts. included were Hep.BsAg and HIV negative. M e t h o d s : A l l pts. had serum alan/he (ALT) and aspartate (AST) aminotransferases measured at biopsy. Only 1 pt. required a repeat liver biopsy on account of inadequate liver tissue at initial biopsy. All biopsies were assessed blindly by a hiatopathologist who graded the inflammatory and fibrotie changes, giving a score 0 for normal or non-specific changes,1 for chronic persistent hepatitis (CPH),2 for mild chronic active hepatitis (CAH), 3 for moderate CAH, 4 for severe CAH and 5 for cirrhosis. Results:83% pts.were asymptomatic, while the remainder had mild flu like . symptoms with occasional jaundice preceding liver biopsy. None had signs of chronic liver disease.' 14 pts. had a normal ALT (<33lull), 20 pts. had a normal AST (<35/u/I). 24 pts. had ALT >2x normal, while only 12 pts.had AST >2x normal.(Mean ALT=126iu/1,65-392);(Mean AST=84iu/l,70-170). There were 5 normal liver biopsies,6 CPH's,20 mild CAH's,12 moderate CAH's,2 severe CAH's and .2 cirrhotics. There was no correlation between the lack of symptoms 'and' normal histology, while the presence of symptoms predicted either C A H or cirrhosis in all cases. When the population was reviewed as a whole there was a significant correlation (p<0.05);(R>0.3) between the transaminases and histology. However, there was no significant correlation between normal transaminases and histology. While the positive predictive value of a normal ALT/AST was equally poor in predicting normal histology (0.2). the positive predictive value of 2x normal ALT/AST was equally good at predict/he either CAH. or cirrhosis (0.9). However there was no linear correlation between the level of transaminitis and the degree of CAH. or cirrhosis. Conclusion: The presence . of symptoms and/or raised transaminases predicts 90% of CAH or cirrhosis. The absence of symptoms and/or normal transaminases unfortunately does not predict normal histology. No linear correlation exism, between the degree of transaminitis and histological activity. Thus we recommend histological assessment in all HCV IVDA's.
• DOSE INCREASE AUGMENTS THE RESPONSE RATE TO INTEP, FERON-
I
•
HEPATITIS NON-ABC. IS THERE YET ANOTHER POST TRANSFUSION HEPATITIS (Fill)? S.V Feinman*, M. Blajclmaan2, S. BulP, J, Dienstagz, E. L Heathcote 4, G. Minuk s, E. Schroeder~, 1The Liver Study Unit and Lunenfeld Res. Inst., Mount Sinai Hospital, Univ. of Toronto.2 Dept. of Pathology, McMaster Univ, Hamilton, Out; ZMass. Gem Hospital - Boston, Mass, U.S:A., *Toronto'Hospital Toronto, Ont., SHealth Science Centre - Winnipeg, Man., Canada. Background: In 2 PTH studies, (1,2) a large number of Pts. with ALT levels
compatible with PTH were negative for markers of A, B, and C. Methods: 576 and 4,588 blood recipients were followed. Controls: 688 recipients of autologous blood (Lancet in press). All Pts. with hepatitis were tested for hepatitis A,B,C, EBV and, CMV and for HCV RNA by RT PeR using primers of 5' NC region. Results: Sex: M:F = 13:13. 17 Pts. recovered. The ALT levels ranged flora I01 U. to 1,125 U (N < 40). 4 Pts. were lost to follow-up. 2 Pts. progressed to chronic hepatitis with ALT elevation lasting up to 4 years. 3 had liver biopsies: 2 had chronic hepatitis and 1 had steatosis and chronic inflammation. Repeated tests for Anti-HCV and HCV RNA were negative. None of the 5 recipients of autologous blood progressed to chronic hepatitis. Timeof
1983- 1985 1988- 1/5190 (BeforeAnfi-HCV) 215/90-31/1193
(Afteranti-HCV) t9ss ~ 3'~93 (Aulologoes)
Tota!
post Trattsfusloanepaflts B C ~ C
0
18.(3.1%)
34 (6.1%)
799
10 (1.25%)
0
5 (0.63%)
5 (0.63%)"
3.789
29 (0.77*70)
O
8 (0.21%)
21 (0.55%)
658
5 (0.7o%)
0
o
s (0.7o%)
Numberof ~ents
576
52 (9.2*7o)
Conclusions: The PTH incidence in Canada declined from 9.2% in 83/85 to 0.85%
in 88/93. Sixty-five percent in 83/85 and 67% in 88/93 were Non-ABC. The marked decline of PTH Nou-ABC from 6.1% in 83/85 to 0.6% in 88/93 parallels the decline of Hepatitis C and suggest an infections etiology. Introduction of Ami-HCV testing had no effect on the incidence of Hepatitis Non-ABe. The fact that Hepatitis NonABC was present in recipients of autologons blood suggests that it may not be tranffusion related. It may represent either a nosocomial or community acquired infection. Non-viral causes are a possibility as well. Considering the fact that 5 of 22 Pts with Hepatitis Non-ABC (23%) progressed to chronicity warrants further studies including attempts to identify the infectious agent(s).
• ~ OF A/J MICE WITH METHYI2PaIANISOLONE (MP) CAUSES LOSS OF RESISTANCE TO MURINE HEPAa',','-SVIRUS STRAIN 3 (~RV-3) AND FinqeroteI, JL ieibowitz , YS Rao , C~ Levy , Dept. of Medicine, University of Toronto, Toronto, Ont. 2De~t~. of Pathology, University of Texas, Houston, Texas. Following infection with MHV-3, BALB/cJ mice die of fulminant hepatitis whereas A/J mice develop no clinical, histological or biochemical evidence of liver injury. Susceptibility correlates with inductio~ of increased macrophage PCA secondary to synthesis of a unique prothrcmbinase geoe, mouse fihr~Kxgen-like protein (~fiblp). Tnis study was undertaken to determine the effect of MP on induction of ~ in vitro and resistance to ~RV-3 in rive. Peritoneal macrc~mhages were~harvested from A/J mice and incubated with MP prior to exposure to ~RV-3. PCA in these oells demonstrated MP dose dependent increases in functional PCA, whereas no PCA was detected in macrophages infecTx~ with MHV-3 or treated'with MP alone. Analysis of m~NA transcripts for musfiblp demonstrated increased m~NA levels in MP treated and ~{V-3 infected A/J macr-q0hagesas compared to macrophages not incubated with MP prior to MHV-3 infection. A/J mioe, treated with MP prior to exposure to i0n plaque forming units of ~4V-3, died within i0 days of exposure with histological findings of hepatocyte necrosis and hepatic s/nusoidal fibrin deposition, increased MHV-3 replication and elevated liver enzymes (peak alanine transaminase: 1500+450 IU/L). These studies demonstrate that treatment with MP is associated with loss of resistance to MHV-3 in A/J mice and 'induction of musfiblp transcription with expression of increased functional P(~. These results provide further evidence for a critical role of PCA induction in the pathogenesis of MHV-3 related liver injury. This work was supported by Program Project Grant 11810 from the Medical Research Council of Canada.
AASLD ABSTRACTS
Correlation between Symptoms, Aminotransferases Liver Histology in I . V . D . A . H e p a t i t i s C pts.
GASTROENTEROLOGY,VoI. IO8, No. 4
and
RI.Farrell.I.Khan.M.Malonev.J.Farrell.GSA.MeDonald*.PWN.Keelin ~. Dept, of Gastroenterology & Pathology*,gt.James's Hospital, Dublin 8, Ireland. Object: To assess the correlation between the clinical, biochemical and histologieal activity in intravenous drug related Hepatitis C pts. Patients:47 IVDA's who were diagnosed HCV.positive according to the Ortho EIA,UBI EIA and RIBA '3 tests were referred for liver biopsy. The male:female ratio was 2il,mean age was 28.Syrs., mean interval betweenHCV testing and liver biopsy was 5.1 mths.with a mean length of IVDA.preceding HCV testing of 7.6 yrs. Pts. with an alcohol consumption >14u./wk. for females .and >21u./wk.for males was excluded from review. All pts. included were Hep.BsAg and HIV negative. M e t h o d s : A l l pts. had serum alan/he (ALT) and aspartate (AST) aminotransferases measured at biopsy. Only 1 pt. required a repeat liver biopsy on account of inadequate liver tissue at initial biopsy. All biopsies were assessed blindly by a hiatopathologist who graded the inflammatory and fibrotie changes, giving a score 0 for normal or non-specific changes,1 for chronic persistent hepatitis (CPH),2 for mild chronic active hepatitis (CAH), 3 for moderate CAH, 4 for severe CAH and 5 for cirrhosis. Results:83% pts.were asymptomatic, while the remainder had mild flu like . symptoms with occasional jaundice preceding liver biopsy. None had signs of chronic liver disease.' 14 pts. had a normal ALT (<33lull), 20 pts. had a normal AST (<35/u/I). 24 pts. had ALT >2x normal, while only 12 pts.had AST >2x normal.(Mean ALT=126iu/1,65-392);(Mean AST=84iu/l,70-170). There were 5 normal liver biopsies,6 CPH's,20 mild CAH's,12 moderate CAH's,2 severe CAH's and .2 cirrhotics. There was no correlation between the lack of symptoms 'and' normal histology, while the presence of symptoms predicted either C A H or cirrhosis in all cases. When the population was reviewed as a whole there was a significant correlation (p<0.05);(R>0.3) between the transaminases and histology. However, there was no significant correlation between normal transaminases and histology. While the positive predictive value of a normal ALT/AST was equally poor in predicting normal histology (0.2). the positive predictive value of 2x normal ALT/AST was equally good at predict/he either CAH. or cirrhosis (0.9). However there was no linear correlation between the level of transaminitis and the degree of CAH. or cirrhosis. Conclusion: The presence . of symptoms and/or raised transaminases predicts 90% of CAH or cirrhosis. The absence of symptoms and/or normal transaminases unfortunately does not predict normal histology. No linear correlation exism, between the degree of transaminitis and histological activity. Thus we recommend histological assessment in all HCV IVDA's.
• DOSE INCREASE AUGMENTS THE RESPONSE RATE TO INTEP, FERON-
I
•
HEPATITIS NON-ABC. IS THERE YET ANOTHER POST TRANSFUSION HEPATITIS (Fill)? S.V Feinman*, M. Blajclmaan2, S. BulP, J, Dienstagz, E. L Heathcote 4, G. Minuk s, E. Schroeder~, 1The Liver Study Unit and Lunenfeld Res. Inst., Mount Sinai Hospital, Univ. of Toronto.2 Dept. of Pathology, McMaster Univ, Hamilton, Out; ZMass. Gem Hospital - Boston, Mass, U.S:A., *Toronto'Hospital Toronto, Ont., SHealth Science Centre - Winnipeg, Man., Canada. Background: In 2 PTH studies, (1,2) a large number of Pts. with ALT levels
compatible with PTH were negative for markers of A, B, and C. Methods: 576 and 4,588 blood recipients were followed. Controls: 688 recipients of autologous blood (Lancet in press). All Pts. with hepatitis were tested for hepatitis A,B,C, EBV and, CMV and for HCV RNA by RT PeR using primers of 5' NC region. Results: Sex: M:F = 13:13. 17 Pts. recovered. The ALT levels ranged flora I01 U. to 1,125 U (N < 40). 4 Pts. were lost to follow-up. 2 Pts. progressed to chronic hepatitis with ALT elevation lasting up to 4 years. 3 had liver biopsies: 2 had chronic hepatitis and 1 had steatosis and chronic inflammation. Repeated tests for Anti-HCV and HCV RNA were negative. None of the 5 recipients of autologous blood progressed to chronic hepatitis. Timeof
1983- 1985 1988- 1/5190 (BeforeAnfi-HCV) 215/90-31/1193
(Afteranti-HCV) t9ss ~ 3'~93 (Aulologoes)
Tota!
post Trattsfusloanepaflts B C ~ C
0
18.(3.1%)
34 (6.1%)
799
10 (1.25%)
0
5 (0.63%)
5 (0.63%)"
3.789
29 (0.77*70)
O
8 (0.21%)
21 (0.55%)
658
5 (0.7o%)
0
o
s (0.7o%)
Numberof ~ents
576
52 (9.2*7o)
Conclusions: The PTH incidence in Canada declined from 9.2% in 83/85 to 0.85%
in 88/93. Sixty-five percent in 83/85 and 67% in 88/93 were Non-ABC. The marked decline of PTH Nou-ABC from 6.1% in 83/85 to 0.6% in 88/93 parallels the decline of Hepatitis C and suggest an infections etiology. Introduction of Ami-HCV testing had no effect on the incidence of Hepatitis Non-ABe. The fact that Hepatitis NonABC was present in recipients of autologons blood suggests that it may not be tranffusion related. It may represent either a nosocomial or community acquired infection. Non-viral causes are a possibility as well. Considering the fact that 5 of 22 Pts with Hepatitis Non-ABC (23%) progressed to chronicity warrants further studies including attempts to identify the infectious agent(s).
• ~ OF A/J MICE WITH METHYI2PaIANISOLONE (MP) CAUSES LOSS OF RESISTANCE TO MURINE HEPAa',','-SVIRUS STRAIN 3 (~RV-3) AND FinqeroteI, JL ieibowitz , YS Rao , C~ Levy , Dept. of Medicine, University of Toronto, Toronto, Ont. 2De~t~. of Pathology, University of Texas, Houston, Texas. Following infection with MHV-3, BALB/cJ mice die of fulminant hepatitis whereas A/J mice develop no clinical, histological or biochemical evidence of liver injury. Susceptibility correlates with inductio~ of increased macrophage PCA secondary to synthesis of a unique prothrcmbinase geoe, mouse fihr~Kxgen-like protein (~fiblp). Tnis study was undertaken to determine the effect of MP on induction of ~ in vitro and resistance to ~RV-3 in rive. Peritoneal macrc~mhages were~harvested from A/J mice and incubated with MP prior to exposure to ~RV-3. PCA in these oells demonstrated MP dose dependent increases in functional PCA, whereas no PCA was detected in macrophages infecTx~ with MHV-3 or treated'with MP alone. Analysis of m~NA transcripts for musfiblp demonstrated increased m~NA levels in MP treated and ~{V-3 infected A/J macr-q0hagesas compared to macrophages not incubated with MP prior to MHV-3 infection. A/J mioe, treated with MP prior to exposure to i0n plaque forming units of ~4V-3, died within i0 days of exposure with histological findings of hepatocyte necrosis and hepatic s/nusoidal fibrin deposition, increased MHV-3 replication and elevated liver enzymes (peak alanine transaminase: 1500+450 IU/L). These studies demonstrate that treatment with MP is associated with loss of resistance to MHV-3 in A/J mice and 'induction of musfiblp transcription with expression of increased functional P(~. These results provide further evidence for a critical role of PCA induction in the pathogenesis of MHV-3 related liver injury. This work was supported by Program Project Grant 11810 from the Medical Research Council of Canada.