Chronic Hepatitis B with Fanconi’s Syndrome Triggered by Short-term Administration of Adefovir Dipivoxil

Abstract

The patient was a 45-year-old man who had Down syndrome and hepatitis B virus (HBV) with a high virus load and the presence of hepatitis B e antigen. He had received lamivudine (100mg/day: per os) as nucleoside/ nucleotide analogues (NAs) from April 2005 to December 2012. Although the initial response of HBV DNA was favorable, a high level of viral breakthrough without hepatitis reactivation occurred after 16 -months of lamivudine administration. In December 2012, the therapy with lamivudine was substituted with adefovir dipi‐ voxil (ADV) and entecavir hydrate (ETV) after informed consent was obtained. Serum HBV DNA gradually decreased over 7 -months of this drug substitution; however, there was a gradual increase in the serum alkali‐ phosfatase (ALP) level without increase in the other hepatobiliary enzymes and nephrotoxicity. Since he was suspected as having drug-induced liver damage and nephropathy caused by NAs, ADV and ETV were adminis‐ tered every other day for 3 months, resulting in no improvement. The laboratory data was obtained in December 2013 as follows; peak 3 dominant in the ALP isoenzyme analysis, low levels of serum carcium, phosphorus and urinary acid, excessive urinary excretion of amino acid and increased level of serum creatinine. Thus, we sug‐ gested that he suffered from acquired Fanconi’s syndrome induced by ADV. Administration of ADV was then discontinued after 12 months of drug substitution and only ETV was prescribed. Six months after ADV discon‐ tinuation, some of the indicative markers of renal dysfunction, including Fanconi’s syndrome, were normalized and recovered to the same levels before the combined use of ADV and ETV. The patient had been treated with sodium valproate and carbamazepine for the unstable mental state and epilepsy before the lamivudine adminis‐ tration; however, the negative synergic action among these drugs and NAs was not evaluated sufficiently. Here, we report the earlier onset of Fanconi’s syndrome triggered by ADV, which is usually diagnosed after long-term ADV administration. We suggest that the adequate evaluation of renal function, including proximal tubular damage before administration of ADV and close observation from the early period during treatment with ADV, is required.