Association Between Liver Fibrosis/Cirrhosis and ALT Levels
Ira M. Jacobson, MD:
Elevated ALT levels and liver histology indicative of fibrosis are often major factors in the decision to initiate antiviral therapy for chronic HBV infection. A growing body of literature has shown that HBV-infected patients with normal ALT levels often have considerable liver fibrosis. A study by Goebel and colleagues retrospectively analyzed the relationship between fibrosis and ALT levels in non-Asian patients with chronic HBV infection (Capsule Summary). The investigators examined liver histology in 252 patients with various ALT levels, including a substantial cohort with normal ALT levels, and showed that the incidence of cirrhosis on liver biopsy was similar between patients with normal vs elevated ALT levels. Among patients with ALT 2 times the upper limit of normal (n = 130). Significant inflammation, however, was less common in patients with normal ALT levels (26%) compared with those with elevated ALT levels (52% to 68%), but I think most experienced clinicians would treat all viremic patients with cirrhosis or advanced fibrosis, regardless of the level of inflammation.
One strength of this study is the use of definitions of normal ALT that are more consistent with current thinking than those provided by commercial labs. Specifically, the ULN was defined as 23 IU/L in males, which is actually even slightly lower than the 30 IU/L that is the current recommendation, and 19 IU/L in females. A limitation of the study is that although not explicitly stated in the abstract, ALT appears to have been assayed at only a single time point, whereas it would have been a more robust analysis if based on a differentiation of patients with persistently normal. Nevertheless, the results add to a growing body of literature suggesting that guidelines for treatment of hepatitis B should reconsider the significance of ALT levels in determining candidacy for treatment.
Jules L. Dienstag, MD:
Several recent studies have suggested that many patients with normal ALT levels have substantial scarring of the liver, but there are also many studies in the literature, most of which are older, showing that many patients with normal ALT levels have very mild or no liver disease when biopsied. This study represents a cohort of patients who were referred to a liver center, as is the case for several other studies; therefore, a referral bias may have resulted in a selection of patients with more severe disease in this study. Some of the earlier studies showing very little disease in patients with low ALT levels were performed in clinical cohorts in which the patients may not have been quite as highly selected.
Clearly, however, clinicians cannot be entirely optimistic about HBV-infected patients with normal ALT levels. The true frequency of severe disease in these patients is likely to lie somewhere between the high rates that have been published recently and the low rates reported in the past.
Robert G. Gish, MD:
I am a strong supporter of assessing liver disease in patients with normal ALT levels. I am cautiously enthusiastic about the potential use of transient elastography in this setting, which may provide a more acceptable option for both doctors and patients who are reluctant to consider liver biopsy in this setting. Several reports at this meeting suggested that transient elastography is reliable in hepatitis B, including data suggesting that the assessment of fibrosis was not impacted by the presence of fatty liver.[40-43 ]
Jules L. Dienstag, MD:
Even when clinicians decide not to biopsy patients with normal ALT levels, these patients should be monitored closely, and the decision to biopsy can often be made at a later time point. The important point is that, whether these patients are biopsied immediately or not, they should be followed carefully.
this post is of corse not to scare but for correct managment of hbv infection whichis already in the guidelines:
hbvdna,alt and biopsy or fibroscan all needed for very very accurate image of hbv infection, hbsag when available can also help distinguish inactive carriers from cronic hbv carrier during inactive phase and also those with very high chances of hbv eradication by interferons
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