Published online Apr 14, 2013. doi: 10.3748/wjg.v19.i14.2256
Revised: January 18, 2013
Accepted: February 5, 2013
Published online: April 14, 2013
AIM: To investigate whether the disease progression of chronic hepatitis C patients with normal alanine aminotransferase (ALT) levels differs by ALT levels.
METHODS: A total of 232 chronic hepatitis C patients with normal ALT (< 40 IU/L) were analyzed. The patients were divided into “high-normal” and “low-normal”ALT groups after determining the best predictive cutoff level associated with disease progression for each gender. The incidence of disease progression, as defined by the occurrence of an increase of ≥ 2 points in the Child-Pugh score, spontaneous bacterial peritonitis, bleeding gastric or esophageal varices, hepatic encephalopathy, the development of hepatocellular carcinoma, or death related to liver disease, were compared between the two groups.
RESULTS: Baseline serum ALT levels were associated with disease progression for both genders. The best predictive cutoff baseline serum ALT level for disease progression was 26 IU/L in males and 23 IU/L in females. The mean annual disease progression rate was 1.2% and 3.9% for male patients with baseline ALT levels ≤ 25 IU/L (low-normal) and > 26 IU/L (high-normal), respectively (P = 0.043), and it was 1.4% and 4.8% for female patients with baseline ALT levels ≤ 22 IU/L (low-normal) and > 23 IU/L (high-normal), respectively (P = 0.023). ALT levels fluctuated during the follow-up period. During the follow-up, more patients with “high-normal” ALT levels at baseline experienced ALT elevation (> 41 IU/L) than did patients with “low-normal” ALT levels at baseline (47.7% vs 27.9%, P = 0.002). The 5 year cumulative incidence of disease progression was significantly lower in patients with persistently “low-normal” ALT levels than “high-normal” ALT levels or those who exhibited an ALT elevation > 41 U/L during the follow-up period (0%, 8.3% and 34.3%, P < 0.001).
CONCLUSION: A “high normal” ALT level in chronic hepatitis C patients was associated with disease progression, suggesting that the currently accepted normal threshold of serum ALT should be lowered.
Core tip: Recent studies have indicated that the upper limit of normal for the serum alanine aminotransferase (ALT) level should be lowered. However, outcome studies based on the development of adverse events during long-term follow-up are limited. In this present study, among patients infected with chronic hepatitis C virus who had normal ALT levels, the risk of disease progression differed between patients with “high-normal” and “low-normal” ALT levels, even within the currently accepted normal levels. This finding suggests that lowering the normal threshold of ALT levels may be necessary to better identify patients who are at increased risk for disease progression.