Unique Characteristics Associated with Sustained Liver Damage in Chronic Hepatitis C Patients Treated with Direct Acting Antivirals

Abstract

Background and Aims: Direct-acting antivirals (DAAs) dramatically improve the sustained virological response (SVR) of chronic hepatitis C (CHC) patients. However, continuous liver damage after SVR may be a risk of hepatocellular carcinoma (HCC). We clarified pretreatment characteristics related to sustained liver damage after SVR. Methods: A total of 286 CHC patients were treated with an interferon-free DAA regimen. Among them, 250 patients achieved SVR for 12 weeks after the end of treatment (SVR12); these individuals were classified based on α-fetoprotein (AFP) and alanine transaminase (ALT) levels posttreatment. Baseline characteristics significantly associated with AFP >5 ng/mL and ALT level ≥20 IU/L after SVR were clarified using multivariate analyses. Results: Among the pretreatment factors examined, serum AFP values and the presence of fatty liver (FL) were significantly associated with abnormal AFP (p < 0.0001) and ALT levels 12 weeks after SVR12 (SVR24; p = 0.0109). For 126 patients who showed an increase in baseline AFP level, FL, fibrosis-4 (FIB-4) index, and albumin levels before treatment were related to abnormal AFP at SVR24 (p = 0.0005, 0.0232, and 0.0400 for FL, FIB-4 index, and albumin, respectively). Similarly, for 150 patients with abnormal baseline ALT levels, FL was associated with an ALT level ≥ 30 IU/L after SVR (p = 0.0430). Conclusions: High FIB-4 index, low albumin level, and FL before DAA treatment were associated with a risk of sustained liver damage with AFP and ALT elevation after SVR; patients with these factors should be carefully monitored for emergence of HCC.

Risk of hepatocellular carcinoma after hepatitis C virus cure

“…Moreover, patients with LS without advanced fibrosis had higher rates of mortality and HCC compared to those with advanced fibrosis but without steatosis[ 42 ]. Kono et al [ 44 ] concluded in their study of 286 CHC patients that fatty liver along with advanced liver fibrosis is associated with sustained liver damage with abnormal alpha-feto protein (AFP) and ALT levels even after HCV cure. In a prospective study conducted by Noureddin et al [ 45 ], 47.5% of the HCV patients with SVR had evidence of LS.…”

HCC occurrence after DAA treatments: molecular tools to assess the post-treatment risk and surveillance

“…Multivariate analysis identified pre-treatment low albumin levels and fibrosis 4 (FIB-4) index as independent predictive factors for the sustained AFP after SVR. At the same time, the fatty liver presence was associated with both sustained abnormal AFP and ALT levels after SVR [8] suggesting that the persistence of hepatocyte damage and regeneration mechanisms might lead to HCC development. The oxidative stress present in the fatty liver might also be responsible for DNA damage that foster carcinogenesis [8].…”

“…At the same time, the fatty liver presence was associated with both sustained abnormal AFP and ALT levels after SVR [8] suggesting that the persistence of hepatocyte damage and regeneration mechanisms might lead to HCC development. The oxidative stress present in the fatty liver might also be responsible for DNA damage that foster carcinogenesis [8]. Confirming the results of Kono et al, Watanabe et al identified FIB-4 index ≥4.0 and albumin ≤3.8 g/dl at the beginning of DAA treatment and a FIB-4 index ≥4.0 and AFP ≥6.0 at the end of DAA treatment as independent predictors for HCC occurrence [9].…”