Frequent Liver Function Tests Can Detect Transient ALT Increases in Chronic Hepatitis B Patients

By Liz Highleyman

Over years or decades, a proportion of people with chronic hepatitis B virus (HBV) infection will develop advanced liver disease, including cirrhosis and hepatocellular carcinoma. But not everyone develops these complications, and most experts advise that individuals with non-progressive liver disease do not require antiviral treatment.

A liver biopsy is the "gold standard" for determining the extent of liver damage, but on an ongoing basis, clinicians monitor levels of the liver enzymes alanine and aspartate transaminase (ALT and AST), which indicate liver inflammation. Levels are typically measured every 6 to 12 months. It is often assumed that people with normal ALT have stable disease with minimal liver damage and therefore don't need treatment.

Liver Biopsy

As reported in the January 16, 2009 advance online issue of Gastroenterology, Indian researchers evaluated the frequency and factors that predict spontaneous ALT increases in 217 asymptomatic hepatitis B "e" antigen (HBeAg) negative, anti-HBe positive chronic hepatitis B patients with normal ALT at study entry.

Spontaneous increases in ALT levels (ALT "flares") were considered to be > 2 times the upper limit of normal and were accompanied by HBV DNA levels of at least 100,000 copies/mL or a 100-fold increase from the previously measured level.

Results

During a median follow-up period of 69 months, 43 patients experiences spontaneous ALT flares, for an annual rate of 4.3%.

The cumulative probabilities of experiencing ALT flares were 10.8% after 5 years and 47.3% after 10 years.

The median time to a spontaneous ALT flare after study enrollment was 25 months (range 1-128 months).

In a multinomial logistic regression analysis, the probability of an ALT flare was correlated with age > 30 years at presentation (odds ratio [OR] 5.31; P = .008), male sex (OR 4.54; P = .05), and presence of a pre-core mutation (OR 10.99; P < .001).

The investigators suggested that unidentified transient ALT flares are probably more common than suspected in asymptomatic hepatitis B patients, and advised that follow-up ALT monitoring every 3 months "can capture up to 90% of flares and would help identify patients who require antiviral therapy."

Department of Gastroenterology, G. B. Pant Hospital, New Delhi, India; Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; Department of Pathology, G. B. Pant Hospital, New Delhi, India.

3/20/09

Reference
M Kumar, R Chauhan, N Gupta, and others. Spontaneous increases in alanine aminotransferase levels in asymptomatic chronic hepatitis B virus-infected patients with normal ALT. Gastroenterology. January 16, 2009 [Epub ahead of print].