Clinical impact of normal alanine aminotransferase on direct‐acting antiviral outcome in patients with chronic hepatitis C virus infection

BACKGROUND AND AIMS: This study aimed to clarify the clinical picture of hepatitis C virus (HCV) carriers with normal alanine aminotransferase (CNALT) and those with ALT elevation (non‐CNALT) under direct‐acting antivirals (DAAs). METHODS: We enrolled 1002 patients with HCV (427 men, median age: 69 years) who had received DAAs for comparisons between CNALT (ALT ≤33 U/L in males and ≤25 U/L in females; n = 374) and non‐CNALT (n = 628) groups. RESULTS: CNALT patients displayed a higher platelet count (PLT) (170 000 vs 146 000/μL, P < 0.0001) and albumin (4.1 vs 4.1 g/dL, P = 0.0006) but lower AST (25 vs 51 U/L, P < 0.0001), alpha fetoprotein (3.2 vs 5.4 ng/mL, P < 0.0001), and liver fibrosis marker scores (all P < 0.0001). The sustained virologic response rate was comparable between the CNALT and non‐CNALT groups (97.8 vs 95.3%, P = 0.106). The cumulative incidence of hepatocellular carcinoma (HCC) after DAA treatment was comparable between the CNALT and non‐CNALT groups (P = 0.117, log‐rank test). In CNALT patients with HCC history, PLT ≥150 000/μL was an independent risk factor of HCC recurrence (P = 0.019). In non‐CNALT patients without HCC history, male gender (P = 0.021) and albumin <4.0 g/dL (P = 0.007) were independent risk factors, while PLT < 150 000/μL (P = 0.081) was a marginal risk factor of HCC occurrence. CONCLUSION: CNALT patients displayed a milder degree of liver fibrosis. Combinations of CNALT and PLT status might be useful as markers for HCC occurrence or recurrence surveillance.