SERUM HCV-RNA, ALT LEVELS AND AST/ALT RATIO DO NOT PREDICT SEVERITY OF LIVER DISEASE IN CHRONIC HEPATITIS C VIRUS INFECTION

Author: DW Reedy, AT Loo, RA Levine. Division of Gastroenterology, SUNY Health Science Center, Syracuse, NY

The presence or absence of cirrhosis and the degree of liver inflammation in chronic HCV infection are criteria which influence the intent to treat. AST/ALT ratio of >= 1 has been reported as having a calculated 100% positive predictive value for cirrhosis (Gastroenterology 1996; 110: A1322). If the need for a liver biopsy could be obviated and the severity of liver disease predicted based on defined clinical and biochemical parameters, then the cost of health care could be reduced.

Methods: We evaluated 89 patients, including 18 cirrhotics, to determine if the degree of liver inflammation and presence of cirrhosis could be predicted based solely on correlation with serum HCV-RNA, ALT and AST levels. All patients denied heavy alcohol use within 4 months of evaluation. Using a modified Knodell score, hepatic activity index (HAI), reflecting histologic inflammation (summation of labour, periportal and portal inflammation), was graded by 2 investigators who assessed the biopsies blinded. HAI was correlated by linear regression with ALT, AST, and HCV-RNA levels, the latter determined by quantitative PCR (AMPLICOR-Roche). Results: In noncirrhotics vs cirrhotics, there was no significant difference between mean ALT (173 vs 161), AST (103 vs 139) and HCV-RNA (560,765 vs 531,994) levels, respectively (Student t test). Mean HAI was significantly lower in the cirrhotic (HAI = 6.2) vs the noncirrhotic group (HAI = 7.9, P < 0.02). There was no correlation between HAI and HCV-RNA, ALT and AST levels within either the noncirrhotic or cirrhotic groups. AST/ALT ratio in noncirrhotics was <= 1 in 57/60 and >= 1 in only 3/60. In cirrhotics, AST/ALT ratio was <= 1 in 11/18 and >= 1 in 7/18 patients. The positive predictive value of a ratio >= 1 for cirrhosis was only 69%.

Conclusions: Our results show that AST/ALT ratio, although specific for the presence of cirrhosis, had only a modest positive predictive value and  should not be the sole determinant to identify cirrhosis. Liver biopsy should be performed prior to treatment of chronic HCV infection, since HCV-RNA, ALT and AST levels fail to predict accurately the severity of liver inflammation or the presence of cirrhosis.

Reference: American Association for the Study of Liver Diseases - 1996
Annual Meeting