In the Journals

Sofosbuvir, ribavirin prevented recurrent HCV infection after liver transplant

Sofosbuvir and ribavirin administered before liver transplantation prevented posttransplantation recurrence of hepatitis C infection, according to new research data.

“Patients with hepatitis C virus at the time of liver transplantation (LT) universally experience recurrent HCV infection,” Michael P. Curry, MD, from Beth Israel Deaconess Medical Center in Boston, said in a press release. “Recurrent HCV infection follows an aggressive course. Given the burden of disease — the increased morbidity, mortality and costs — and the lack of a safe and broadly effective treatment to prevent recurrence of HCV infection, these results provide hope for patients in need.”

Curry and colleagues performed a phase 2 open-label study involving 61 patients with HCV and cirrhosis who were on waitlists for LT for hepatocellular carcinoma (HCC). They received once-daily 400 mg sofosbuvir (Sovaldi, Gilead) and ribavirin before LT for up to 48 weeks or until time of LT (median, 21 [range, 2.3-52.3] weeks) to prevent HCV recurrence after LT.

Forty-six patients received of LT, 43 of whom had HCV RNA level less than 25 IU/mL at the time of LT. Of those 43 patients, 70% achieved post-LT virologic response at 12 weeks (49% of overall cohort), 23% had recurrent HCV infection and 7% died (two from nonfunction of primary graft and one from complications of hepatic artery thrombosis). Number of consecutive days HCV RNA level was undetectable and found to be a predictor of post-LT virologic response; patients with recurrent infection had a median of 5.5 days (range, 0-88 days) with undetectable HCVRNA level compared with 99.5 (range, 1-473 days) for patients with post-LT virologic response (P<.001). The most frequently reported adverse events were fatigue (38%), headache (23%) and anemia (21%).

“Because of the small size of this study, any conclusions must be considered preliminary in nature and require further evaluation in larger studies,” the researchers wrote.

In an accompanying editorial, Alessio Aghemo, MD, PhD, and Maria Francesca Donato, MD, from the A.M. Migliavacca Center for Liver Disease at the University of Milan, characterized these findings as “a major medical breakthrough … because they provide convincing proof that a 24-week course of [sofosbuvir plus ribavirin] can eliminate HCV infection in two-thirds of patients, with obvious positive consequences on their short- and long-term prognoses. For clinicians, this is also a breakthrough because it provides a safe and easy approach to manage medical treatment that is devoid of all the complications, management nuances, and ultimately the indirect costs that were required to manage [interferon]-containing regimens.” 

For more information:

Aghemo A. Gastroenterology. 2015;148:13-16.

Curry P. Gastroenterology. 2015;148:100-107.

Disclosure: Many of the researchers report financial ties with Gilead. See the study for a full list of relevant financial disclosures. Aghemo reports financial ties with AbbVie and Merck, and both Aghemo and Donato report financial ties with Gilead and Janssen.

Sofosbuvir and ribavirin administered before liver transplantation prevented posttransplantation recurrence of hepatitis C infection, according to new research data.

“Patients with hepatitis C virus at the time of liver transplantation (LT) universally experience recurrent HCV infection,” Michael P. Curry, MD, from Beth Israel Deaconess Medical Center in Boston, said in a press release. “Recurrent HCV infection follows an aggressive course. Given the burden of disease — the increased morbidity, mortality and costs — and the lack of a safe and broadly effective treatment to prevent recurrence of HCV infection, these results provide hope for patients in need.”

Curry and colleagues performed a phase 2 open-label study involving 61 patients with HCV and cirrhosis who were on waitlists for LT for hepatocellular carcinoma (HCC). They received once-daily 400 mg sofosbuvir (Sovaldi, Gilead) and ribavirin before LT for up to 48 weeks or until time of LT (median, 21 [range, 2.3-52.3] weeks) to prevent HCV recurrence after LT.

Forty-six patients received of LT, 43 of whom had HCV RNA level less than 25 IU/mL at the time of LT. Of those 43 patients, 70% achieved post-LT virologic response at 12 weeks (49% of overall cohort), 23% had recurrent HCV infection and 7% died (two from nonfunction of primary graft and one from complications of hepatic artery thrombosis). Number of consecutive days HCV RNA level was undetectable and found to be a predictor of post-LT virologic response; patients with recurrent infection had a median of 5.5 days (range, 0-88 days) with undetectable HCVRNA level compared with 99.5 (range, 1-473 days) for patients with post-LT virologic response (P<.001). The most frequently reported adverse events were fatigue (38%), headache (23%) and anemia (21%).

“Because of the small size of this study, any conclusions must be considered preliminary in nature and require further evaluation in larger studies,” the researchers wrote.

In an accompanying editorial, Alessio Aghemo, MD, PhD, and Maria Francesca Donato, MD, from the A.M. Migliavacca Center for Liver Disease at the University of Milan, characterized these findings as “a major medical breakthrough … because they provide convincing proof that a 24-week course of [sofosbuvir plus ribavirin] can eliminate HCV infection in two-thirds of patients, with obvious positive consequences on their short- and long-term prognoses. For clinicians, this is also a breakthrough because it provides a safe and easy approach to manage medical treatment that is devoid of all the complications, management nuances, and ultimately the indirect costs that were required to manage [interferon]-containing regimens.” 

For more information:

Aghemo A. Gastroenterology. 2015;148:13-16.

Curry P. Gastroenterology. 2015;148:100-107.

Disclosure: Many of the researchers report financial ties with Gilead. See the study for a full list of relevant financial disclosures. Aghemo reports financial ties with AbbVie and Merck, and both Aghemo and Donato report financial ties with Gilead and Janssen.