title: Disease progression in chronic hepatitis C patients with normal alanine aminotransferase levels.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Sanggye Paik Hospital, Inje University School of Medicine, Seoul 139-707, South Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Sinn
authors.forename: Geum-Youn
authors.initials: GY
authors.lastname: Gwak
authors.forename: Jae-Uk
authors.initials: JU
authors.lastname: Shin
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Choi
authors.forename: Joon Hyeok
authors.initials: JH
authors.lastname: Lee
authors.forename: Kwang Cheol
authors.initials: KC
authors.lastname: Koh
authors.forename: Seung Woon
authors.initials: SW
authors.lastname: Paik
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoo
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004796:Clinical Enzyme Tests / Q000592:standards; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012016:Reference Values; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D000410:Alanine Transaminase
keywords: Alanine aminotransferase; Disease progression; Hepatitis C virus; Hepatocellular carcinoma; Upper limits of normal