Hepatitis C Virus Clearance Is Associated With the Improvement of the Branched-Chain Amino Acid to Tyrosine Ratio (BTR) of Patients With Mild-To-Advanced Fibrosis

The progression of chronic hepatitis caused by hepatitis C virus (HCV) is associated with abnormalities in amino acid metabolism. We aimed to characterise the changes in free amino acid (FAA) in the peripheral blood of HCV patients undergoing direct antiviral agents (DAAs). We retrospectively enrolled 183 HCV patients: 116 without hepatocellular carcinoma (HCC) treated with DAAs, and 67 with HCC (19 were treated with DAAs and 48 were not). Biochemical parameters, including 20 FAAs, were measured at four time points (before treatment, at SVR12, at SVR24, and at last follow-up) between 2006 and 2022. The mean observation period was 54 ± 25 months for patients without HCC and 42 ± 26 months for those with HCC. We examined the relationships among the branched-chain amino acid to tyrosine ratio (BTR) and clinical factors. Propensity score matching (PSM) was performed to compare outcomes in HCC patients who achieved sustained virological response (SVR) with those who did not. This was a retrospective study with no dietary intervention, and subgroup analyses were limited by sample size. In non-HCC patients, BTR significantly increased 12 weeks post-SVR and continued to increase throughout follow-up. This improvement was more marked in patients with advanced fibrosis. The changes in tyrosine were inversely correlated with those of M2BPGi, whereas those in BCAA were not. In HCC patients, those achieving SVR maintained their BTR, whereas untreated patients showed significant deterioration. After PSM, similar improvements in FAA imbalances occurred in post-SVR HCC patients. Clearance of HCV is associated with improvement of the BTR across patients with mild to advanced fibrosis or successfully treated HCC, suggesting that gradual recovery of amino acid imbalance reflects improved nutritional status.