Biopsy Is Required To Evaluate Liver Disease Severity and Decide When To Begin Therapy

Liver Biopsy: study finds 55% (19/34) with normal or close to normal ALT with chronic HCV started HCV therapy based on biopsy (17% had bridging fibrosis or cirrhosis)

It is still believed by some that the ALT level in HCV infected person is  adequate to predict severity of liver disease including whether or not cirrhosis is present. It remains controversial but I believe the data and research strongly supports that biopsy must be done to make a reliable evaluation of a person's stage of liver disease. Here is a relevant abstract from the DDW 1999 Conference. But there have been other studies supporting this notion.

The Histologic Spectrum of Chronic Hepatitis C in Patients with Repeatedly Normal ALT (Alanine Aminotransferase): Does Liver Biopsy Make a Difference?
     Angela Nutt, UAMS, Little Rock Arkansas; H Hassan, J Lindsey, L Lamps, J-P Raufman

The Most recent NIH Consensus Conference Panel on the management of hepatitis C (Hepatology 1997; 26:2S) recommends that "treatment of patients with persistently normal ALT is not beneficial". Nevertheless, the rationale for this approach in this subset of patients has not been substantiated. The Panel suggests that "serial determinantions of ALT levels over time may provide a better means of assessing liver injury", but admits "the accuracy of this approach has not been really shown".

Our experience with many HCV infected individuals with repeatedly normal ALT values and histologically advanced liver disease prompted us to examine systematically liver histology in this subset of patients. Using the following criteria, we sequentially identified 34 patients at our institution (University Hospital of Arkansas and McClellan Memorial VA) between 1996 and 1998: (1) HCV-RNA positive by rt-PCR and, (2) At least 2 ALT determinations during the six months prior to liver biopsy and all values 1.4 times the upper limit of normal (50 IU/I).

Liver biopsies were evaluated and graded (Knodell et al. Hepatology 1981; 1:431) by a hepatopathologist (LL) who was unaware of the ALT values. The 34 patients (6 females, 28 males), meeting the above criteria  {age 25 to 69 yrs (mean + SD, 44.5 plus/minus 8.7 yrs)} had a mean ALT of 38.2 plus or minus 13.1 IU/I (range, 7-66 IU/I). Seventy-four percent had normal (<5) and 18 (52%) had moderate to marked portal inflammation (I'm not sure this is worded correctly, or I'm not sure I exactly understand this sentence). Regarding advanced liver disease, 8.8% (3/34) had bridging fibrosis and 8.8% (3/34) had cirrhosis. Of the 34 patients, 19 (55%) were started on antiviral therapy based on these results.

In summary, in these 34 patients with chronic HCV and normal or near normal ALT, 52% had significant portal inflammation, and an additional 17% had bridging fibrosis or cirrhosis. In conclusion, this study demonstrates that patients with chronic HCV and repeatedly normal ALT may have histologically advanced liver disease and should be considered for HCV therapy. It also indicates that liver biopsy is useful for making therapeutic decisions in all patients with chronic HCV.