Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report

Abstract

The United States Food and Drug Administration recently warned that the direct acting antiviral (DAA) combination hepatitis C virus (HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin (PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis (compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment with Hasin Y et al . HCV cures after DAA-related drug-induced liver injury PODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.

Modeling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct‐acting antiviral agents

“…We next compared model predictions to data of viral load changes in two patients who achieved EOT + /SVR following DAA‐based therapy of ultra‐short durations10, 11 (see Methods). We assumed that the restoration of exhausted CTLs was negligible in the short period during therapy (~3 weeks) and fit the resulting reduced, basic model of viral kinetics to the data during therapy.…”

“…Future studies may reveal whether such measurements during the treatment of chronic infection in humans bear signatures of the reversal of exhaustion and hence can be analyzed to estimate the unknown parameters above. The fraction of patients treated who achieve EOT + /SVR appears to vary widely across treatments and patient populations 3, 5, 6, 7, 8, 9, 10, 11, 12. Weak effector responses and/or inadequate treatment durations may underlie the inability of patients to achieve EOT + /SVR compared to those who do in the latter reports.…”

“…The patient was then lost to follow up until day 475, when viremia was reported undetectable. The second patient was treated with a combination of peritaprevir, ombitasvir, dasabuvir plus ritonavir and ribavirin for 24 days 11. The last reported viral load measurement during therapy was at day 14 from the start of therapy, when viremia was detectable.…”

“…Fitting the reduced model to patient data from one patient10 during treatment then allowed estimation of ε, c , and the composite parameter δ = ω +  mE 0 . With the other patient,11 because of infrequent sampling, we set ε and c to the values obtained above, which were similar to the values estimated elsewhere,18 and fit the data using δ as an adjustable parameter. We performed data fitting using the function NLINFIT in MATLAB.…”

“…Indeed, treatments as short as 3 weeks have been shown to succeed in select populations 4. A promising avenue for such reduction arises from the observation, made by several recent studies, that some patients treated with DAAs had detectable viremia at the end of treatment (EOT) but eventually attained a sustained virological response (SVR), or cure, without additional therapy 3, 5, 6, 7, 8, 9, 10, 11, 12. (Typically, SVR refers to undetectable viremia 12 weeks after the EOT.)…”