hepatitis C immune globulin or antibody product, reduced the likelihood of
hepatitis C virus infecting the new liver graft after transplantation in people who were receiving, but had not yet completed, antiviral treatment,
according to preliminary study findings presented at the European
Association for the Study of the Liver (EASL) 50th International
Liver Congress last month in Vienna, Austria.
Without treatment, hepatitis C virus
(HCV) almost always infects the donor liver after a transplant, and recurrence is the
leading cause of graft loss and liver disease progression. Effective
direct-acting antiviral therapy that leads to sustained virological response
can prevent reinfection, but people receiving antiviral treatment at the time
of transplantation remain at risk.
Norah Terrault of
the University of California at San Francisco and colleagues are conducting an
ongoing randomised phase 3 study (NCT01804829) to evaluate hepatitis C immune globulin (HCIG or Civacir) for prevention of post-transplant HCV recurrence. Civacir, being developed by Biotest
Pharmaceuticals, is a human immune globulin product derived from
hundreds of screened blood donors with high HCV antibody levels. Use of
multiple donors increases antibody diversity and improves its activity against
a variety of HCV strains.
found in the blood and cerebrospinal fluid.
This preliminary analysis, presented as a
late-breaking poster, included 63 people with hepatitis C with advanced liver
disease on the transplant waiting list, enrolled as of late January 2015. More
than 80% were men, most were white and the mean age was 61 years. Most (93%)
had HCV genotype 1, with the rest having genotypes 2 or 3. The median MELD
score was 19, the median Child-Pugh score was 7 and 77% had hepatocellular
carcinoma. People with hepatitis B co-infection and those getting HCV-infected
liver grafts were excluded.
Participants could be taking any antiviral regimen
that resulted in HCV RNA <100 IU/ml within 4 weeks prior to transplantation.
More than 90% received regimens containing sofosbuvir (Sovaldi), including 63% taking sofosbuvir plus ribavirin and 21%
taking sofosbuvir plus simeprevir (Olysio);
the rest used various interferon-containing regimens.
Treatment had been ongoing for a median of 64 days,
or just over 9 weeks, at the time of transplantation; nearly half had not yet
received the full typical 12-week course of sofosbuvir and none had received
the 24-week course recommended for harder-to-treat patients. Fifteen per cent had detectable
HCV viral load at the time of transplantation.
Participants in this open-label study were
randomly assigned to receive either 200 or 300mg/kg HCIG or else
standard-of-care treatment (antivirals only). Those assigned to HCIG received sixteen
infusions around the time
of transplantation and immediately thereafter for 10 weeks.
results showed that only one out of 21 patients (5%) in the HCIG 300mg/kg arm
experienced HCV reinfection after transplantation. Seven out of 22 people (32%)
in the HCIG 200mg/kg arm and six out of 20 patients (30%) in the control arm experienced
reinfection, indicating that the lower dose performed no better than not using
HCIG at all. Five out of nine patients (55%) who had detectable HCV viral load
in the 200mg/kg and control arms experienced HCV recurrence.
antibody titres remained elevated (around 1.5- to 2-fold higher) in the 300mg/kg HCIG arm relative to the 200mg/kg and control arms, indicating ongoing
protection over the course of the study.
generally safe and well-tolerated, with no drug-related serious adverse events
seen to date. Nine people discontinued treatment early, including three due to
adverse events. The most frequently reported adverse events were related to
underlying liver disease, surgery-associated events and symptoms such as fever known
to be associated with use of human immune globulins.
preliminary results suggest that Civacir 300mg/kg can increase the proportion
of patients on pre-liver transplantation antiviral therapy achieving prevention
of HC recurrence post-liver transplantation," the researchers concluded.
They added that
this evaluation justified continuing enrolment in the 300mg/kg arm, but not in
the 200mg/kg low-dose arm, which has been closed.