SUMMARY: 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.

By Liz Highleyman

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.

HBV 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.

Prolonged 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 EASL.

Results

	3 participants dropped out of the study before the 24-week randomization.
	No participants in either treatment arm experienced recurrence of chronic HBV infection (HBV DNA > 169 copies/mL) while on therapy.
	The researchers reported that no tenofovir-related "safety signals" were observed.
	3 patients discontinued therapy due to adverse events considered related to treatment (increased ALT and worsening ulcerative colitis).
	The rate of serious adverse events was similar in the 2 treatment arms, and none were considered related to tenofovir/emtricitabine.
	Patients receiving HBIG had more grade 3-4 laboratory abnormalities (especially elevated glucose) than those receiving tenofovir/emtricitabine alone.
	Among 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 kidney function.
	4 patients with initially mild kidney impairment at baseline had a confirmed creatinine clearance < 50 mL/min during treatment, but they remained on therapy.
	No participants had a confirmed increase in serum creatinine of ? 0.5 mg/dL or a decrease in phosphorus to < 2 mg/dL.

Tenofovir/emtricitabine "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.

4/20/10

Reference
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 28.