(Truvada) Prevents Hepatitis B Recurrence after Liver Transplantation
in Patients with Mild Kidney Impairment
Combination therapy using tenofovir
(Viread) plus emtricitabine
(Emtriva) -- the 2 drugs in the Truvada
coformulation -- either with or without injected
hepatitis B virus (HBV) antibodies, was well tolerated
and prevented HBV recurrence in chronic hepatitis B
patients with mild-to-moderate kidney (renal) impairment
who underwent liver transplantation, according to a
study presented last week at the 45th Annual Meeting
of the European Association for the Study of the Liver
(EASL 2010) in Vienna.
Over years or decades, chronic hepatitis
B can result in advanced liver disease necessitating a transplant.
Without preventive measures, however, HBV will usually recur and
infect the new donor liver.
vaccination, hepatitis B immune gobulin or antibodies (HBIG),
and prophylactic use of antiviral drugs such as tenofovir can
prevent recurrence; HBIG plus antiviral therapy can reduce the
risk by 90% or more during the first years after transplantation.
administration of HBIG injections is expensive and inconvenient,
however, and researchers have tested whether antiviral drugs alone
can prevent HBV recurrence over the long-term. But tenofovir can
cause kidney toxicity, especially with prolonged use and in individuals
with pre-existing kidney disease or risk factors.
L. Teperman from New York University Medical Center and colleagues
evaluated the safety and efficacy of tenofovir/emtricitabine with
or without HBIG for preventing HBV recurrence after orthotopic
liver transplantation (Gilead Study 107). Tenofovir is currently
approved for treatment of both hepatitis B and HIV, while emtricitabine
is only approved for HIV.
The study enrolled 40 chronic hepatitis B patients receiving HBIG
who were in stable condition 12 or more weeks after receiving
a liver transplant. Most (80%) were men, the median age was 59
years, 38% were Asian, 33% were white, and 25% were black. None
had hepatitis C or HIV coinfection. The median time since liver
transplantation was 3.4 years (range 4 months to 18 years).
At study entry the participants had not yet experienced HBV recurrence
(undetectable HBV DNA viral load and hepatitis B surface antigen
[HBsAg] negative), had not previously used tenofovir for more
than 1 year, and had normal or modestly impaired liver function
with creatinine clearance ? 40 mL/min. They were grouped according
to baseline kidney function according to creatinine clearance:
normal (> 80 mL/min), mild impairment (50-80 mL/min), or moderate
impairment (30-49 mL/min).
Patients were treated with tenofovir/emtricitabine plus HBIG for
24 weeks. At that point, they were randomly assigned (1:1) to
either continue on this combination or to discontinue HBIG and
remain on tenofovir/emtricitabine alone for an additional 72 weeks.
The investigators presented interim results through week 72 at
participants dropped out of the study before the 24-week randomization.
participants in either treatment arm experienced recurrence
of chronic HBV infection (HBV DNA > 169 copies/mL) while
researchers reported that no tenofovir-related "safety
signals" were observed.
patients discontinued therapy due to adverse events considered
related to treatment (increased ALT and worsening ulcerative
rate of serious adverse events was similar in the 2 treatment
arms, and none were considered related to tenofovir/emtricitabine.
receiving HBIG had more grade 3-4 laboratory abnormalities
(especially elevated glucose) than those receiving tenofovir/emtricitabine
patients treated for 72 weeks, median serum creatinine levels
and changes in creatinine were similar in the groups with
normal, mildly impaired, and moderately impaired baseline
patients with initially mild kidney impairment at baseline
had a confirmed creatinine clearance < 50 mL/min during
treatment, but they remained on therapy.
participants had a confirmed increase in serum creatinine
of ? 0.5 mg/dL or a decrease in phosphorus to < 2 mg/dL.
"was well tolerated through week 72 in patients with mild
to moderate renal impairment post orthotopic liver transplant
with appropriate monitoring and dose adjustment," the investigators
concluded. "Notably, no patient has experienced HBV recurrence
including the treatment group that discontinued HBIG and remained
on [tenofovir/emtricitabine] alone."
The Mary Lea Johnson Richards Organ Transplantation Center,
New York University Medical Center, New York, NY; Emory Healthcare,
Atlanta, GA; Cedars-Sinai Medical Center, Los Angeles, CA; Recanati/Miller
Transplantation Institute, Mount Sinai Hospital, New York, NY;
California Pacific Medical Center, San Francisco, CA; Mayo Clinic,
Jacksonville, FL; Schiff Liver Institute, University of Miami,
Miami, FL, Gilead Sciences, Durham, NC.
L Teperman, J Spivey, F Poordad, and others. Emtricitabine/tenofovir
DF combination +/? HBIG post-orthotopic liver transplantation
to prevent hepatitis b recurrence in patients with normal to moderate
renal impairment: interim results. 45th Annual Meeting of the
European Association for the Study of the Liver (EASL 2010). Vienna,
Austria. April 14-18, 2010. Abstract