EFFECTIVENESS OF ADENINE-ARABINOSIDE 5'-MONOPHOSPHATE IN KIDNEY-TRANSPLANT RECIPIENTS WITH CHRONIC ACTIVE HEPATITIS-B

Hepatitis B virus infection is responsible for both morbidity and mortality in kidney transplant recipients. Adenine arabinoside 5'-monophosphate (ARA-AMP), a synthetic purine nucleotide with anti-viral activity, leads to a sustained interruption of HBV replication in approximately 40% of immunocompetent patients. We report the results of a pilot study using ARA-AMP to treat HBV-related chronic active hepatitis in kidney transplant recipients. Ten patients (2 females and 8 males, mean age 44 years, mean time post-transplantation 163 months) received a 28-day course of ARA-AMP intramuscularly: 5 mg/kg twice daily for the first 5 days during hospitalization and subsequently 5 mg/kg once daily at home for the remaining 23 days. Mean follow-up was 18 months, ranging from 7 to 28 months. All patients but one had biopsy-proven chronic hepatitis, including five cases of cirrhosis. All patients had been chronic HBs Ag carriers for more than 1 year and had active replication as assessed by the presence of serum HBV DNA (mean titre, 270 pg/ml, ranging from 12 to 997 pg/ml, Genostics method). HBe Ag was present in 7 of the 10 patients. Pretreatment creatinine was normal. In four of the 10 patients, HBV DNA became undetectable respectively 1, 1, 5, and 11 months after beginning-AR-A-AMP. In five patients, HBV DNA decreased during ARA-AMP therapy but subsequently increased although no change was noted during the follow-up period. In two partial responders, a second 4-week course of ARA-AMP was given 8 and 9 months after the first course, and resulted in a sustained HBV DNA loss 1 and 4 months later: HBV DNA reappeared 3 months later in the former. Two of the responders relapsed with reappearance of HBV replication 2 and 22 months after treatment: HBV DNA disappeared 1 year later in the former. ARA-AMP was well tolerated in nine patients, without side-effects in five and mild muscular pain in four, although one patient complained of severe but reversible peripheral neuropathy. Renal function remained stable in all patients during follow-up. Our results suggest that a 4-week course of ARA-AMP interrupts HBV replication in 40% of kidney recipients with chronic active hepatitis. Repetition of the treatment may enhance the efficacy of ARA-AMP in partial responders. Efficacy and tolerance seem therefore to be at least comparable to what has been previously reported in immunocompetent patients.