Serum Alanine Aminotransferase Level Alone May Not Accurately Represent Necro-Inflammation in Patients with Acute Hepatitis
To the Editor:
We read with interest the article by Arena et al.,1 who suggested that liver stiffness (LS) values could be influenced by necro-inflammation during the acute hepatitis phase. Similarly, Coco et al.2 previously suggested that LS values increase in patients with chronic hepatitis during alanine aminotransferase (ALT) flares.
Arena et al.1 used the ALT level as a marker for the degree of necro-inflammation. They performed LS measurement at three different points according to ALT levels. However, the ALT level may not be a good indicator of the degree of necro-inflammation. Another article, published in the same journal, reported that LS values did not correlate with ALT levels in patients with acute liver damage.3
Recently, we experienced two cases of cholestatic type acute hepatitis A. The patients had no previous personal or family history of liver disease, and they denied excessive alcohol use. They were both positive for immunoglobulin M antibodies to hepatitis A virus.
A 32-year-old man developed jaundice 1 month prior to presentation at our hospital. He was originally admitted to another hospital, at which his ALT and bilirubin levels were found to be 479 IU/L and 14.5 mg/dL, respectively. He was transferred to our hospital after 10 days because his bilirubin level increased to 24.1 mg/dL. The ALT and bilirubin levels recorded at our facility were 36 IU/L and 30.3 mg/dL, respectively. Liver biopsy showed mild necrotic and inflammatory activity with no fibrosis (METAVIR score, A1F0; Fig. 1A). However, the LS value was 9.9 kPa. The bilirubin level normalized after 3 months, and at that time, the LS value decreased to 5.5 kPa.
A 23-year-old man developed jaundice 1 month prior to presentation at our hospital. He was originally admitted to another hospital. Upon admission to that facility, his ALT and bilirubin levels were 153 IU/L and 16.8 mg/dL, respectively. He was transferred to our hospital after 1 month because his bilirubin level increased to 22.2 mg/dL. The ALT and bilirubin levels at the time of liver biopsy were 72 IU/L and 30.1 mg/dL, respectively. Liver biopsy showed moderate necro-inflammatory activity with fibrous portal expansion (METAVIR score, A2F1; Fig. 1B). The LS value was 26.0 kPa. The bilirubin level was normalized after 3 months, and at that time, the LS value decreased to 5.5 kPa.
Although our patients had low ALT levels (≤2 times the upper limit of normal) and no or mild fibrosis on liver biopsy, LS values were high, and they decreased to 5.5 kPa after normalization of bilirubin levels. This disagreed with the results of Arena et al.'s study,1 in which LS values were normalized in all patients except for one when ALT levels were reduced to ≤2 times the upper limit of normal.
We wholly agree with Arena et al.' consideration that acute necro-inflammation could influence LS values.1, 2 However, the ALT level alone may not accurately represent the degree of necro-inflammation, which influences LS values. Therefore, when we interpret LS measurement results in chronic hepatitis patients experiencing acute exacerbations, we should consider not only ALT but bilirubin and other markers of necro-inflammation as well.
1Arena U, Vizzutti F, Corti G, Ambu S, Stasi C, Bresci S, et al. Acute viral hepatitis increases liver stiffness values measured by transient elastography. HEPATOLOGY2008; 47: 380–384.
2Coco B, Oliveri F, Maina AM, Ciccorossi P, Sacco R, Colombatto P, et al. Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat2007; 14: 360–369.
3Sagir A, Erhardt A, Schmitt M, Haussinger D. Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. HEPATOLOGY2008; 47: 592–595.
Yeon Seok Seo*, Soon Ho Um*, Eun Suk Jung*, Hyung Joon Yim*, Chang Duck Kim*, Ho Sang Ryu*, * Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.