Sofosbuvir-based regimens, with or without daclatasvir, greatly improve the clinical status of patients who develop fibrosing cholestatis hepatitis (FCH) after liver transplantation for hepatitis C virus (HCV) infection, and most of the patients achieve a sustained virologic response (SVR), researchers report in the November issue of Clinical Gastroenterology and Hepatology. These results are likely to change the prognosis for patients with FCH.
FCH develops with HCV recurrence after liver transplantation. It is characterized by rapid portal fibrosis and cholestasis, leading to rapid deterioration of the liver graft. Patients develop severe jaundice, coagulopathy, encephalopathy, and have increased serum levels of bilirubin. FCH occurs in 2%–10% of liver recipients, and the prognosis is very poor—50% to 90% of patients die within 2 years.
FCH is believed to be caused by the cytotoxic effects of HCV under conditions of immunosuppression. Studies have shown that liver transplant recipients who achieve an SVR to therapy have longer survival times. Vincent Leroy et al therefore evaluated the efficacy and safety of sofosbuvir-based regimens in patients with FCH after liver transplantation.
They analyzed data from 23 patients who participated in a prospective study in France and Belgium. Most of the patients had genotype 1 infections that had not responded to previous treatment; 4 patients also were infected with HIV.
Within a median time of 5 months after liver transplantation, patients received sofosbuvir and daclatasvir (n = 15) or sofosbuvir and ribavirin (n = 8) for 24 weeks. The primary outcome was complete clinical response (survival without re-transplantation, bilirubin level <34 μmol/L, and no ascites or hepatic encephalopathy 36 weeks after treatment began).
All patients were alive without re-transplantation at week 36. Dramatic improvements in liver function parameters were observed, and 22 patients (96%) had a complete clinical response (see figure).
The patients’ median bilirubin concentration decreased from 122 μmol/L at baseline to a normal value at week 12 of treatment. The only patient with hepatic encephalopathy recovered at week 12, and ascites disappeared from 7 of 8 patients.
Twenty-two patients (96%) had an SVR at 12 weeks after stopping treatment (SVR12), despite the fact that most had high baseline viral loads and slow virologic responses to therapy. In the sofosbuvir and daclatasvir group the rate of SVR12 was 100%. The only relapse of HCV infection occurred in a patient with HIV infection who received sofosbuvir and ribavirin.
In an editorial that accompanies the article, Jeanne-Marie Giard and Norah A. Terrault highlight the outcomes of 4 patients with HIV co-infection. In co-infected patients, recurrence of HCV disease is accelerated, cholestatic hepatitis is more frequent, and graft losses occur more often than in patients with only HCV infection. The finding that 3 of these 4 patients achieved an SVR indicates that severe cholestatic disease is manageable in most patients co-infected with HIV and HCV.
Drug tolerance was satisfactory, with no grade 3 or 4 adverse events related to sofosbuvir or daclatasvir and no significant interactions among drugs.
Leroy et al conclude that antiviral therapy should begin as early as possible after a diagnosis of FCH. Even earlier therapy could be considered for patients with risk factors for FCH, such as an older donor, HIV co-infection, or early recurrence of HCV infection with high levels of HCV RNA.