A Mathematical Model of Hepatitis C Virus Dynamics in Patients With High Baseline Viral Loads or Advanced Liver Disease

Background & AimsPatients with baseline hepatitis C virus-RNA levels (bHCV-RNA) > 6 log IU/mL or cirrhosis have a reduced probability of a sustained-virologic response (SVR). We examined the relation between bHCV-RNA, cirrhosis, and SVR with a mathematical model that includes the critical-drug efficacy (ϵc; the efficacy required for a drug to clear HCV), the infection-rate constant (β), and the percentage of HCV-infected hepatocytes (π).MethodsThe relation between baseline factors and SVR was evaluated in 1000 in silico HCV-infected patients, generated by random assignment of realistic host and viral kinetic parameters. Model predictions were compared with clinical data from 170 noncirrhotic and 75 cirrhotic patients.ResultsThe ranges chosen for β and the viral production rate (p) resulted in bHCV-RNA levels that were in agreement with the distribution observed in US patients. With these β and p values, higher bHCV-RNA levels led to higher ϵc, resulting in lower SVR rates. However, higher β values resulted in lower bHCV-RNA levels but higher π and ϵc, predicting lower rates of SVR. Cirrhotic patients had lower bHCV-RNA levels than noncirrhotic patients (P = .013), and more had bHCV-RNA levels < 6 log IU/mL (P < .001). Even cirrhotic patients with lower bHCV-RNA levels had lower SVR rates. An increase in β could explain the results observed in cirrhotic patients.ConclusionsOur model predicts that higher bHCV-RNA levels lead to higher ϵc, reducing the chance of achieving SVR; cirrhotic patients have lower SVR rates because of large π values, caused by increased rates of hepatocyte infection.