Bile Acids and Heptatitis
Serum Total Bile Acids Level As A Sensitive Prognostic Test for HCV Patients Treated with Interferon
Toshihide Sima et al.(J. Gastroenterol. hepatol. 15: 294-299,2000) recently reported that serum TBA levels is a sensitive indicator of hepatic histological improvement in chronic hepatitis C patients responding to interferon treatment. A decrease in serum TBA levels reflects histological improvement in the liver more precisely than changes of other liver function test values following Interferon therapy (IFN). IFN has been widely used for treatment of chronic hepatitis C virus (HCV) infection since the late 1980s and is still the most approved treatment for chronic hepatitis C. Approximately one-third of IFN-treated patients with chronic hepatitis C show long-term favorable responses, including the eradication of HCV, normalization of liver function test values, and improvement in liver histology. TBA has been revealed to be more sensitive than other conventional live function tests (ALT, AST, GGT total bilirubin, albumin, and colinesterase (ChE)) in detecting liver dysfunction, and the monitoring of TBA has been reported to be useful for determining the clinical course of chronic liver diseases. For example, in patients with whom compensated liver cirrhosis was progressing into the decompensated form, TBA levels increased before changes in other liver function test values occurred. During the course of IFN treatment for HCV patients, various liver function tests including serum TBA were performed and the sensitivities of these tests in responding to interferon treatment were compared (See Figures 6a to 6d). Data in Figure 8 depict the changes of test values before and after IFN treatment separated by groups of the all responders (•), responders with mild chronic active hepatitis (°), and severe chronic active hepatitis (Δ).
Prognostic use of Serum Total Bile Acids Level In Hepatitis
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As seen in Figure 8a, and 8b, there were no Differentiations in values ofALT and GGT between mild and severe chronic hepatitis. |
In contrast, serum TBA values (Figure8c) clearly differentiate mild chronic active hepatitis from severe chronic active hepatitis, indicating that serum TBA is a more sensitive indicator predicting the severeness of liver dysfunction. |
More importantly, none of the conventional liver function tests (ALT, AST, GGT, albumin, bilirubin, and ChE) show any correlation with patient’s liver histological improvements following IFN therapy. ALT and AST values indicate hepatocellular necrosis and GGT value reflects both cholestasis and hepatocellular injuries. These conventrional liver function markers significantly decreased and normalized during the first 6 months of IFN treatment, whereas the grading scores of histological activity indices (HAI) were still elevated at the end of a 6 months treatment period as shown in Figure 8d. The HAI grading score (n) and staging scores (®) decreased gradually over the 3 year follow-up period, and its patient matched well with the serum TBA values which also gradually decreased during the 3 year follow-up period. For patients with abnormal TBA values before IFN treatment, there was a significant correlation between the histological improvement in grading scores and serum TBA levels. The TBA value more accurately reflects the overall state of the liver as compared to other liver function tests, so a slow improvement in TBA value suggests that the functional and histological recovery of the damaged liver may extend over a few years, even after the eradication of HCV. Therefore, for severe chronic active hepatitis patients who had an abnormal TBA value before IFN treatment, it is clear that the change in TBA levels is the most sensitive biochemical indicator of hepatic histological improvement after successful IFN treatment for chronic hepatitis C. Hence, prognostic testing of serum TBA provides valuable information on the effectiveness of IFN treatment and the degree of liver histological improvement during and after treatment.
